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Alberti G, Cantillo T, Pereira A, De Barbieri F, García C, Villarroel L, Gana JC. Prevalence of fatty pancreas and its relation with anthropometric values on the Growth and Obesity Cohort Study. J Pediatr (Rio J) 2025; 101:362-369. [PMID: 39657903 PMCID: PMC12039379 DOI: 10.1016/j.jped.2024.09.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Revised: 09/26/2024] [Accepted: 09/27/2024] [Indexed: 12/12/2024] Open
Abstract
OBJECTIVE Nonalcoholic Fatty Pancreas Disease (NAFPD) is characterized by excessive lipid accumulation within the pancreas in the absence of alcohol intake, potentially leading to pancreatic dysfunction and metabolic complications, including type 2 diabetes mellitus, acute and chronic pancreatitis, and pancreatic carcinoma. The authors aim to estimate the prevalence of NAFPD and its association with anthropometric parameters in a cohort of Chilean adolescents. METHOD The authors conducted a cross-sectional analysis of the "Growth and Obesity Chilean Cohort Study" (GOCS), a longitudinal study involving nearly 1000 children, followed yearly since 2006. All participants underwent anthropometric measurements and abdominal ultrasonography. RESULTS A total of 741 adolescents were included; 30 exhibited ultrasonography findings compatible with fatty pancreas (4 %). Adolescents with NAFPD had higher BMI z-score (2.33 (1.52-2.69) vs 0.67 (-0.2-1.4), p < 0.001), waist circumference (WC) (90.9 (81.53-98.58) vs 72.2 (67.55-79.83), p < 0.001), waist-to-height ratio (0.55 (0.48-0.6) vs 0.44 (0.41-0.49), p < 0.001), triponderal index (17.35 (15.14-19.25) vs 13.62 (12.07-15.54), p < 0.001), subcutaneous fat (32.4 (21.77-44.95) vs 16.2 (9.3 - 25.3), p < 0.001), visceral fat (45.15 (36.92-62.08) vs 35.5 (28.55-44.25), p < 0.001), systolic blood pressure (p = 0.009), and diastolic blood pressure but only in boys (p = 0.004) compared with controls. The prevalence of liver steatosis was significantly higher in the NAFPD group (63.3% vs 5.2 %, p < 0.001). After adjusting for sex and BMI, only the association with waist circumference and liver steatosis remains statistically significant. CONCLUSION In adolescents, NAFPD has a prevalence of 4 % and is associated with a higher BMI z-score, WC, superficial fat, and blood pressure levels. Liver steatosis exhibited a strong association with NAFPD.
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Affiliation(s)
- Gigliola Alberti
- Department of Pediatric Gastroenterology and Nutrition, Division of Pediatrics, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | | | - Ana Pereira
- Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de Chile, Santiago, Chile
| | - Florencia De Barbieri
- Radiology Department, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Cristian García
- Radiology Department, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Luis Villarroel
- Department of Public Health, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Juan Cristóbal Gana
- Department of Pediatric Gastroenterology and Nutrition, Division of Pediatrics, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
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Qu H, Zhou L, Tang D, Zhang Q, Yang P, Yang B, Shi J. Relationship between liver fat, pancreatic fat, and new-onset type 2 diabetes mellitus in patients with metabolic dysfunction-associated fatty liver disease. Acta Diabetol 2025:10.1007/s00592-025-02501-7. [PMID: 40252104 DOI: 10.1007/s00592-025-02501-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2024] [Accepted: 03/22/2025] [Indexed: 04/21/2025]
Abstract
PURPOSE Type 2 diabetes mellitus (T2DM) is associated with ectopic fat deposition, especially in the liver and pancreas. Therefore, this study aimed to evaluate the relationship between liver fat fraction (LFF), pancreatic fat fraction (PFF), and new-onset T2DM in metabolic dysfunction-associated fatty liver disease (MAFLD) by magnetic resonance imaging (MRI). METHODS This is a retrospective study of patients with MAFLD who underwent abdominal MRI between 2022 and July 2024. LFF and PFF were measured using an axial multi-echo Dixon-based sequence. All participants underwent routine medical history, anthropometric measurements, and laboratory tests. Multivariable stepwise selection models were constructed to predict PFF and T2DM status based on variables of clinical interest. RESULTS This study included 80 MAFLD patients with 40 untreated new-onset T2DM and 40 non-T2DM controls. LFF, PFF, and homeostasis model assessment of insulin resistance (HOMA-IR) index were higher in the T2DM group than in the control group. In the new-onset T2DM group, PFF was linearly positively correlated with LFF (rs = 0.321, P = 0.04) and HOMA-IR (rs = 0.350, P = 0.03). After adjustment for several metabolic variables, PFF remained an independent risk factor for incident T2DM in MAFLD patients (all P < 0.05). The area under the receiver operating characteristic curve for PFF and LFF to predict T2DM was 0.889 and 0.633 (P < 0.001 and P = 0.03), respectively. CONCLUSION In MAFLD patients, PFF, and LFF play a prominent role in new-onset T2DM with high predictive and diagnostic value.
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Affiliation(s)
- Huanjia Qu
- Department of Endocrinology, Affiliated Hospital of Hangzhou Normal University, Hangzhou, 310015, China
| | - Lingling Zhou
- Department of Endocrinology, Affiliated Hospital of Hangzhou Normal University, Hangzhou, 310015, China
| | - Dong Tang
- Department of Radiology, Affiliated Hospital of Hangzhou Normal University, Hangzhou, 310015, China
| | - Qiuling Zhang
- Department of Endocrinology, Affiliated Hospital of Hangzhou Normal University, Hangzhou, 310015, China
| | - Pu Yang
- Department of Endocrinology, Hangzhou Normal University, Hangzhou, 310000, China
| | - Boyi Yang
- Department of Endocrinology, Hangzhou Normal University, Hangzhou, 310000, China
| | - Junping Shi
- Department of Metabolic Disease Center, Affiliated Hospital of Hangzhou Normal University, Hangzhou, 310015, China.
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Bahrizadeh M, Fotros D, Chegini M, Sadeghi A, Hekmatdoost A, Yari Z. Association of dietary glycemic index and glycemic load with pancreatic steatosis: a case control study. BMC Endocr Disord 2025; 25:89. [PMID: 40165222 PMCID: PMC11956228 DOI: 10.1186/s12902-025-01909-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Accepted: 03/17/2025] [Indexed: 04/02/2025] Open
Abstract
BACKGROUND Carbohydrate intake, its type and characteristics including glycemic index (GI) and glycemic load (GL) may be associated with the risk of pancreatic steatosis (PS), but there is no conclusive evidence. The aim of the present study was to investigate whether the intake of carbohydrates, GI and GL were associated with an increased risk of PS. METHODS To conduct this study, 278 patients with common bile duct stones (CBD) underwent endoscopic ultrasound, including 89 patients with PS (case group) and 189 healthy individuals (control group). In addition to demographic and anthropometric information, a 168-item questionnaire of food frequency was completed to calculate GL and GI. RESULTS With the increase of GI and GL, the number of patients with PS increased significantly (P = 0.013, P < 0.001, respectively) and the risk of PS increased significantly. A similar increase in risk of PS was found with increased risk of carbohydrate, simple sugar and fructose intake. After adjusting all the confounders, the risk of PS with increasing simple sugar and fructose intake was 4.3 times (OR T3 vs. T1 = 4.3, 95% CI: 1.7-10.6, P trend < 0.001) and 5.3 times (OR T3 vs. T1 = 5.3, 95% CI: 2.2-12.9, P trend < 0.001), respectively, compared to the first tertile. Conversely, increased fiber intake showed a reverse association with the PS, so that those in the second and third tertiles of fiber intake were 84% (OR = 0.16, 95% CI: 0.05-0.45) and 87% (OR = 0.13, 95% CI: 0.04-0.39) less at risk of developing PS, respectively (P trend = 0.001). CONCLUSIONS These findings support the hypothesis of direct associations between GI and GL increased risk of PS.
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Affiliation(s)
- Mohammad Bahrizadeh
- Student Research Committee, Department of Clinical Nutrition and dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Department of Clinical Nutrition and dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, West Arghavan St. Farahzadi Blvd., Sharake Qods, Tehran, Iran
| | - Danial Fotros
- Department of Clinical Nutrition and dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, West Arghavan St. Farahzadi Blvd., Sharake Qods, Tehran, Iran
| | - Maedeh Chegini
- Department of Clinical Nutrition and dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, West Arghavan St. Farahzadi Blvd., Sharake Qods, Tehran, Iran
| | - Amir Sadeghi
- Research Institute for Gastroenterology and Liver Diseases of Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Azita Hekmatdoost
- Department of Clinical Nutrition and dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, West Arghavan St. Farahzadi Blvd., Sharake Qods, Tehran, Iran.
| | - Zahra Yari
- Department of Nutrition Research, National Nutrition and Food Technology Research Institute, Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, West Arghavan St. Farahzadi Blvd., Sharake Qods, Tehran, Iran.
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Souza M, Silva GP, Junior CRO, Amaral MJM, Lima LCV, Charatcharoenwitthaya P. Prevalence, clinical characteristics, and outcomes of fatty pancreas disease: an updated systematic review and meta-analysis. Eur J Gastroenterol Hepatol 2025; 37:137-146. [PMID: 39589806 DOI: 10.1097/meg.0000000000002893] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2024]
Abstract
Fatty pancreas disease (FPD) is a condition characterized by diffuse excessive intrapancreatic fat deposition with relevant metabolic implications but often overlooked by healthcare professionals. Our study aims to provide a comprehensive overview of the prevalence, clinical characteristics, and outcomes of FPD. PubMed and Embase databases were searched from inception to 10 April 2024. Pairwise meta-analysis was performed using the DerSimonian-Laird method. Meta-analysis of proportions was conducted using the inverse-variance method with logit transformation. Between-study heterogeneity was examined, with subsequent subgroup and meta-regression analyses, and publication bias was assessed. Eighteen studies with 111 682 individuals were included in this meta-analysis. The overall prevalence of FPD was 21.11% [95% confidence interval (CI): 11.04-36.58]. Diagnostic method influenced FPD prevalence ( P < 0.01), with pooled prevalences of 17.53% (95% CI: 16.20-18.95), 30.05% (95% CI: 24.14-36.70), and 21.23% (95% CI: 8.52-43.88) for MRI, computed tomography, and transabdominal ultrasound, respectively. Patients with FPD were more likely to be older, have higher BMI, male, and have metabolic dysfunction. They also had an increased risk of metabolic syndrome, endocrine-related outcomes (i.e. diabetes and glycemic progression), and exocrine-related outcomes (i.e. acute pancreatitis and pancreatic cancer) compared with those without FPD. This study summarizes the epidemiology of FPD and highlights its clinical and prognostic significance. Increased multidisciplinary collaboration is needed to improve understanding of the disease and raise awareness among healthcare professionals. This study was a priori registered in International Prospective Register of Systematic Reviews (PROSPERO) (CRD42024514116).
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Affiliation(s)
- Matheus Souza
- Department of Internal Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Gabriel P Silva
- Department of Internal Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Carlos R O Junior
- Department of Internal Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Marcio J M Amaral
- Department of Internal Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Luan C V Lima
- Department of Internal Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Phunchai Charatcharoenwitthaya
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
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Li J, Chen Y, Li S, Lyu G, Yan F, Guo J, Cheng J, Chen Y, Lin J, Zeng Y. NAFPD exacerbation by hyperlipidemia combined with hyperuricemia: a pilot rat experiment in lipidomics. Front Nutr 2025; 11:1437373. [PMID: 39839297 PMCID: PMC11746073 DOI: 10.3389/fnut.2024.1437373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2024] [Accepted: 12/18/2024] [Indexed: 01/23/2025] Open
Abstract
Background Hyperuricemia and non-alcoholic fatty pancreas disease (NAFPD) are prevalent metabolic diseases, but the relationship between them remains underexplored. Methods Eighteen Sprague-Dawley rats were randomly assigned to three groups: normal (CON), high-fat (PO), and high-fat high-uric acid (PH). After 12 weeks, serum uric acid (SUA) and triacylglycerol levels were measured. Pathological changes in the pancreas were assessed using hematoxylin-eosin (HE) staining. Serum samples were analyzed using lipidomics technology, and multivariate statistical analysis was employed to identify differences in lipid metabolism. Results SUA levels in the PO group were not significantly different from those in the CON group (p > 0.05). However, from the 4th week onward, SUA levels in the PH group were significantly higher than those in both the PO and CON groups (p < 0.05). HE staining revealed that most rats in the CON group exhibited normal pancreatic islet and acinar cell morphology. The pathological NAFPD score in the PH group was higher than that in the PO group. Lipidomics analysis identified 34 potential serum biomarkers in the CON and PO groups, 38 in the CON and PH groups, and 32 in the PH and PO groups. These metabolites primarily included sphingolipids, cholesterol esters, fatty acids, triacylglycerols, phosphatidylcholines, lysophosphatidylcholine, phosphatidylethanolamine, and lysophosphatidylethanolamine. Conclusion Hyperlipidemia combined with hyperuricemia might exacerbates NAFPD. Glycerophospholipids may serve as key biomarkers in this process, potentially linked to a chronic inflammatory response mediated by glycerophospholipids.
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Affiliation(s)
- Jingyun Li
- Department of Ultrasound, Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China
- Department of Medical Imaging, Quanzhou Medical College, Quanzhou, Fujian, China
| | - Yongjian Chen
- Department of Ultrasound, Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China
| | - Shilin Li
- Department of Ultrasound, Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China
| | - Guorong Lyu
- Department of Ultrasound, Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China
- Department of Medical Imaging, Quanzhou Medical College, Quanzhou, Fujian, China
| | - Furong Yan
- Department of Molecular Diagnostics Research Center, Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China
| | - Jiajing Guo
- Department of Pathology, The 910th Hospital of the People's Liberation Army, Quanzhou, Fujian, China
| | - Jing Cheng
- Department of Animal Experimental Center, Quanzhou Medical College, Quanzhou, Fujian, China
| | - Yun Chen
- Department of Internal Medicine, Quanzhou Medical College, Quanzhou, Fujian, China
| | - Jiaojiao Lin
- Department of Ultrasound, Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China
| | - Yating Zeng
- Department of Ultrasound, Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China
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Dabravolski SA, Churov AV, Elizova NV, Ravani AL, Karimova AE, Sukhorukov VN, Orekhov AN. Association between atherosclerosis and the development of multi-organ pathologies. SAGE Open Med 2024; 12:20503121241310013. [PMID: 39734765 PMCID: PMC11672402 DOI: 10.1177/20503121241310013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Accepted: 12/09/2024] [Indexed: 12/31/2024] Open
Abstract
Atherosclerosis is a chronic inflammatory disease affecting the vascular system, characterised by the accumulation of modified lipoproteins, immune cell aggregation and the development of fibrous tissue within blood vessel walls. As atherosclerosis impacts blood vessels, its adverse effects may manifest across various tissues and organs. In this review, we examine the association of atherosclerosis with Alzheimer's disease, stroke, pancreatic and thyroid dysfunction, kidney stones and chronic kidney diseases. In several cases, the reciprocal causative effect of these diseases on the progression of atherosclerosis is also discussed. Particular attention is given to common risk factors, biomarkers and identified molecular mechanisms linking the pathophysiology of atherosclerosis to the dysfunction of multiple tissues and organs. Understanding the role of atherosclerosis and its associated microenvironmental conditions in the pathology of multi-organ disorders may unveil novel therapeutic avenues for the prevention and treatment of cardiovascular and associated diseases.
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Affiliation(s)
- Siarhei A Dabravolski
- Department of Biotechnology Engineering, Braude Academic College of Engineering, Karmiel, Israel
| | - Alexey V Churov
- Institute of General Pathology and Pathophysiology, Moscow, Russia
- Pirogov Russian National Research Medical University, Russia Gerontology Clinical Research Centre, Institute on Ageing Research, Russian Federation, Moscow, Russia
| | | | | | - Amina E Karimova
- Faculty of Biology and Biotechnology, National Research University Higher School of Economics, Moscow, Russia
| | - Vasily N Sukhorukov
- Institute of General Pathology and Pathophysiology, Moscow, Russia
- Institute of Human Morphology, Petrovsky Russian National Centre of Surgery, Moscow, Russia
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Della Pepa G, Salamone D, Testa R, Bozzetto L, Costabile G. Intrapancreatic fat deposition and nutritional treatment: the role of various dietary approaches. Nutr Rev 2024; 82:1820-1834. [PMID: 38153345 DOI: 10.1093/nutrit/nuad159] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2023] Open
Abstract
Ectopic fat accumulation in various organs and tissues, such as the liver, muscle, kidney, heart, and pancreas, is related to impaired capacity of adipose tissue to accumulate triglycerides, as a consequence of overnutrition and an unhealthy lifestyle. Ectopic fat promotes organ dysfunction and is a key factor in the development and progression of cardiometabolic diseases. Interest in intrapancreatic fat deposition (IPFD) has developed in the last few years, particularly in relation to improvement in methodological techniques for detection of fat in the pancreas, and to growing evidence for the role that IPFD might have in glucose metabolism disorders and cardiometabolic disease. Body weight reduction represents the main option for reducing fat, and the evidence consistently shows that hypocaloric diets are effective in reducing IPFD. Changes in diet composition, independently of changes in energy intake, might offer a more feasible and safe alternative treatment to energy restriction. This current narrative review focused particularly on the possible beneficial role of the diet and its nutrient content, in hypocaloric and isocaloric conditions, in reducing IPFD in individuals with high cardiometabolic risk, highlighting the possible effects of differences in calorie quantity and calorie quality. This review also describes plausible mechanisms by which the various dietary approaches could modulate IPFD.
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Affiliation(s)
- Giuseppe Della Pepa
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
- Cardiometabolic Risk Unit, Institute of Clinical Physiology, National Research Council-CNR, Pisa, Italy
| | - Dominic Salamone
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Roberta Testa
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Lutgarda Bozzetto
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Giuseppina Costabile
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
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Habas E, Farfar K, Habas E, Rayani A, Elzouki AN. Extended Review and Updates of Nonalcoholic Fatty Pancreas Disease. SAUDI JOURNAL OF MEDICINE & MEDICAL SCIENCES 2024; 12:284-291. [PMID: 39539795 PMCID: PMC11556510 DOI: 10.4103/sjmms.sjmms_526_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/12/2023] [Revised: 07/29/2024] [Accepted: 08/01/2024] [Indexed: 11/16/2024]
Abstract
Non-alcoholic fatty pancreatic disease (NAFPD), also known as pancreatic steatosis, is a benign condition characterized by deposition of lipids in the pancreas and is associated with insulin resistance, malnutrition, obesity, metabolic syndrome, aging, and absence of heavy alcohol intake or infection. Similar to nonalcoholic fatty liver disease, NAFPD is a phenotypic entity that includes fat buildup in the pancreas, pancreatic inflammation, and subsequent fibrosis. The extent to which pancreatic fat infiltration is clinically important remains unclear. Despite these clinical associations, most of the clinical effects of NAFPD are not known. NAFPD may be identified by transabdominal and elastography ultrasound, computed tomography scan, or magnetic resonance imaging modalities, but a confirmatory diagnosis can only be made through tissue histology. In addition to complications such as acute and chronic pancreatitis, NAFPD may progress to pancreatic ductal adenocarcinoma. However, further research is required to fully understand the associations, pathophysiology, and effects of NAFPD. This review provides a narrative synthesis of the current literature on the epidemiology, pathophysiology, complications, diagnostic and imaging tools, and management of NAFPD.
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Affiliation(s)
- Elmukhtar Habas
- Department of Medicine, Hamad Medical Corporation, Doha, Qatar
- Department of Medicine, College of Medicine, Qatar University, Doha, Qatar
| | - Kalifa Farfar
- Department of Medicine, Alwakra General Hospital, Alwakra, Qatar
| | - Eshrak Habas
- Department of Medicine, Tripoli Central Hospital, Tripoli, Libya
| | - Amnna Rayani
- Tripoli Children Hospital, Medical College, Tripoli University, Tripoli, Libya
| | - Abdul-Naser Elzouki
- Department of Medicine, Hamad Medical Corporation, Doha, Qatar
- Department of Medicine, College of Medicine, Qatar University, Doha, Qatar
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Pang C, Dong P, Yang J, Fan Z, Cheng Z, Zhan H. Non-alcoholic fatty pancreas disease: an updated review. JOURNAL OF PANCREATOLOGY 2024; 7:212-221. [DOI: 10.1097/jp9.0000000000000157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
Ectopic accumulation of fat can cause a variety of metabolic diseases, and the emerging non-alcoholic fatty pancreas disease (NAFPD) is increasingly being recognized by clinicians as a cause for concern. NAFPD is a disease caused by abnormal accumulation of adipose tissue in the pancreas, which is related to obesity. The main feature of NAFPD is death of acinar cells, which are then replaced by adipose cells. However, the underlying molecular mechanisms have not been fully explored. Obesity, aging, and metabolic syndrome are independent risk factors for the occurrence and development of NAFPD. Studies have shown that NAFPD leads to insulin resistance and pancreatic dysfunction, increases the risk of diabetes mellitus, worsens the severity of pancreatitis, and is significantly correlated with pancreatic cancer and postoperative pancreatic fistula. There is no standard treatment for NAFPD; exercise, a balanced diet, and lifestyle can help reduce pancreatic fat; however, other treatment modalities such as drugs and bariatric surgery are still being explored. The specific pathological mechanism of NAFPD remains unclear, and its potential association with various clinical diseases requires further study. This review summarizes the etiology, diagnosis, clinical consequences, and potential therapeutic strategies of NAFPD.
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Affiliation(s)
- Chaoyu Pang
- Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan 250012, China
| | - Peng Dong
- Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan 250012, China
| | - Jian Yang
- Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan 250012, China
| | - Zhiyao Fan
- Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan 250012, China
| | - Zhiqiang Cheng
- Division of Colorectal Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan 250012, China
| | - Hanxiang Zhan
- Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan 250012, China
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Ookura R, Usuki N, Miki Y. Correlation between Pancreatic Fat Deposition and Metabolic Syndrome: Relationships with Location in the Pancreas and Sex. Intern Med 2024; 63:2113-2123. [PMID: 38171856 PMCID: PMC11358728 DOI: 10.2169/internalmedicine.2450-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Accepted: 11/02/2023] [Indexed: 01/05/2024] Open
Abstract
Objective To investigate the correlation between pancreatic fat deposition and metabolic syndrome (MetS) parameters, focusing on the locations of fat deposition in the pancreas and sex differences. Methods Degrees of fat deposition in the head, body, and tail of the pancreas were evaluated using computed tomography (CT). We examined the relationships between pancreatic fat deposition and the age, body mass index (BMI), visceral and subcutaneous fat, serum lipid profiles, hepatic steatosis, diabetes mellitus (DM), and hypertension (HTN). Results In this retrospective study, greater fat deposition was associated with a higher BMI, visceral and subcutaneous fat accumulation, and hepatic steatosis, with the pancreatic head showing the strongest correlation. Correlations of pancreatic fat deposition with the BMI and visceral and subcutaneous fat accumulation were stronger in females than in males, while correlations with hepatic steatosis were stronger in males than in females. In addition, a multivariate analysis did not suggest a direct causal relationship between pancreatic fat deposition and DM and HTN, but there was a significant correlation between pancreatic fat deposition in the pancreatic head and visceral fat area. Conclusion Pancreatic fat deposition, as evaluated by CT, especially in the part of the pancreatic head adjacent to the ampulla of Vater, is a sensitive indicator of MetS. The correlations between pancreatic fat deposition and MetS parameters tended to be stronger in females than in males. These results may help further elucidate the pathophysiology of MetS and provide opportunities for its diagnosis.
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Affiliation(s)
- Ryusuke Ookura
- Department of Diagnostic and Interventional Radiology, Japan Community Healthcare Organization Osaka Hospital, Japan
- Department of Diagnostic and Interventional Radiology, Graduate School of Medicine, Osaka Metropolitan University, Japan
| | - Noriaki Usuki
- Department of Diagnostic and Interventional Radiology, Japan Community Healthcare Organization Osaka Hospital, Japan
| | - Yukio Miki
- Department of Diagnostic and Interventional Radiology, Graduate School of Medicine, Osaka Metropolitan University, Japan
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Xiao Y, Wang H, Han L, Huang Z, Lyu G, Li S. Predictive value of anthropometric and biochemical indices in non-alcoholic fatty pancreas disease: a cross-sectional study. BMJ Open 2024; 14:e081131. [PMID: 38580356 PMCID: PMC11002413 DOI: 10.1136/bmjopen-2023-081131] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Accepted: 03/22/2024] [Indexed: 04/07/2024] Open
Abstract
OBJECTIVES Triglyceride (TG), triglyceride-glucose index (TyG), body mass index (BMI), TyG-BMI and triglyceride to high-density lipoprotein ratio (TG/HDL) have been reported to be reliable predictors of non-alcoholic fatty liver disease. However, there are few studies on potential predictors of non-alcoholic fatty pancreas disease (NAFPD). Our aim was to evaluate these and other parameters for predicting NAFPD. DESIGN Cross-sectional study design. SETTING Physical examination centre of a tertiary hospital in China. PARTICIPANTS This study involved 1774 subjects who underwent physical examinations from January 2016 to September 2016. PRIMARY AND SECONDARY OUTCOME MEASURES From each subject, data were collected for 13 basic physical examination and blood biochemical parameters: age, weight, height, BMI, TyG, TyG-BMI, high-density lipoprotein (HDL), low-density lipoprotein, total cholesterol, TG, fasting plasma glucose, TG/HDL and uric acid. NAFPD was diagnosed by abdominal ultrasonography. A logistic regression model with a restricted cubic spline was used to evaluate the relationship between each parameter and NAFPD. The receiver operating characteristic (ROC) curve was used to calculate the area under the curve for each parameter. RESULTS HDL was negatively correlated with NAFPD, height was almost uncorrelated with NAFPD and the remaining 11 parameters were positively correlated with NAFPD. ROC curve showed that weight-related parameters (weight, BMI and TyG-BMI) and TG-related parameters (TyG, TG and TG/HDL) had high predictive values for the identification of NAFPD. The combinations of multiple parameters had a better prediction effect than a single parameter. All the predictive effects did not differ by sex. CONCLUSIONS Weight-related and TG-related parameters are good predictors of NAFPD in all populations. BMI showed the greatest predictive potential. Multiparameter combinations appear to be a good way to predict NAFPD.
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Affiliation(s)
- Yang Xiao
- Department of Ultrasonography, Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Han Wang
- Department of Ultrasonography, Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Lina Han
- Department of Ultrasonography, Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Zhibin Huang
- Department of Ultrasonography, Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Guorong Lyu
- Department of Ultrasonography, Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
- Department of Medicine, Quanzhou Medical College, Quanzhou, China
| | - Shilin Li
- Department of Ultrasonography, Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
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12
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Mak AL, Wassenaar N, van Dijk AM, Troelstra M, Houttu V, van Son K, Driessen S, Zwirs D, van den Berg-Faay S, Shumbayawonda E, Runge J, Doukas M, Verheij J, Beuers U, Nieuwdorp M, Cahen DL, Nederveen A, Gurney-Champion O, Holleboom A. Intrapancreatic fat deposition is unrelated to liver steatosis in metabolic dysfunction-associated steatotic liver disease. JHEP Rep 2024; 6:100998. [PMID: 38379586 PMCID: PMC10877191 DOI: 10.1016/j.jhepr.2023.100998] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Revised: 11/21/2023] [Accepted: 12/21/2023] [Indexed: 02/22/2024] Open
Abstract
Background & Aims Individuals with obesity may develop intrapancreatic fat deposition (IPFD) and fatty pancreas disease (FPD). Whether this causes inflammation and fibrosis and leads to pancreatic dysfunction is less established than for liver damage in metabolic dysfunction-associated steatotic liver disease (MASLD). Moreover, the interrelations of FPD and MASLD are poorly understood. Therefore, we aimed to assess IPFD and fibro-inflammation in relation to pancreatic function and liver disease severity in individuals with MASLD. Methods Seventy-six participants from the Amsterdam MASLD-MASH cohort (ANCHOR) study underwent liver biopsy and multiparametric MRI of the liver and pancreas, consisting of proton-density fat fraction sequences, T1 mapping and intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI). Results The prevalence of FPD was 37.3%. There was a clear correlation between pancreatic T1 relaxation time, which indicates fibro-inflammation, and parameters of glycemic dysregulation, namely HbA1c (R = 0.59; p <0.001), fasting glucose (R = 0.51; p <0.001) and the presence of type 2 diabetes (mean 802.0 ms vs. 733.6 ms; p <0.05). In contrast, there was no relation between IPFD and hepatic fat content (R = 0.03; p = 0.80). Pancreatic IVIM diffusion (IVIM-D) was lower in advanced liver fibrosis (p <0.05) and pancreatic perfusion (IVIM-f), reflecting vessel density, inversely correlated to histological MASLD activity (p <0.05). Conclusions Consistent relations exist between pancreatic fibro-inflammation on MRI and endocrine function in individuals with MASLD. However, despite shared dysmetabolic drivers, our study suggests IPFD is a separate pathophysiological process from MASLD. Impact and implications Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide and 68% of people with type 2 diabetes have MASLD. However, fat infiltration and inflammation in the pancreas are understudied in individuals with MASLD. In this cross-sectional MRI study, we found no relationship between fat accumulation in the pancreas and liver in a cohort of patients with MASLD. However, our results show that inflammatory and fibrotic processes in the pancreas may be interrelated to features of type 2 diabetes and to the severity of liver disease in patients with MASLD. Overall, the results suggest that pancreatic endocrine dysfunction in individuals with MASLD may be more related to glucotoxicity than to lipotoxicity. Clinical trial number NTR7191 (Dutch Trial Register).
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Affiliation(s)
- Anne Linde Mak
- Department of Vascular Medicine, Amsterdam University Medical Centers, Amsterdam, The Netherlands
- Amsterdam Gastroenterology Endocrinology Metabolism (AGEM) Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Nienke Wassenaar
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Amsterdam, The Netherlands
- Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, The Netherlands
| | - Anne-Marieke van Dijk
- Department of Vascular Medicine, Amsterdam University Medical Centers, Amsterdam, The Netherlands
- Amsterdam Gastroenterology Endocrinology Metabolism (AGEM) Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Marian Troelstra
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Amsterdam, The Netherlands
| | - Veera Houttu
- Department of Vascular Medicine, Amsterdam University Medical Centers, Amsterdam, The Netherlands
- Amsterdam Gastroenterology Endocrinology Metabolism (AGEM) Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Koen van Son
- Department of Vascular Medicine, Amsterdam University Medical Centers, Amsterdam, The Netherlands
- Amsterdam Gastroenterology Endocrinology Metabolism (AGEM) Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Department of Gastroenterology and Hepatology, Radboudumc, Nijmegen, The Netherlands
| | - Stan Driessen
- Department of Vascular Medicine, Amsterdam University Medical Centers, Amsterdam, The Netherlands
- Amsterdam Gastroenterology Endocrinology Metabolism (AGEM) Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Diona Zwirs
- Department of Vascular Medicine, Amsterdam University Medical Centers, Amsterdam, The Netherlands
| | - Sandra van den Berg-Faay
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Amsterdam, The Netherlands
| | | | - Jurgen Runge
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Amsterdam, The Netherlands
- Department of Radiology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Michail Doukas
- Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Joanne Verheij
- Amsterdam Gastroenterology Endocrinology Metabolism (AGEM) Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Department of Pathology, Amsterdam University Medical Centers, Amsterdam, The Netherlands
| | - Ulrich Beuers
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, Amsterdam, The Netherlands
| | - Max Nieuwdorp
- Department of Vascular Medicine, Amsterdam University Medical Centers, Amsterdam, The Netherlands
- Amsterdam Gastroenterology Endocrinology Metabolism (AGEM) Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Djuna L. Cahen
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Aart Nederveen
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Amsterdam, The Netherlands
| | - Oliver Gurney-Champion
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Amsterdam, The Netherlands
- Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, The Netherlands
| | - Adriaan Holleboom
- Department of Vascular Medicine, Amsterdam University Medical Centers, Amsterdam, The Netherlands
- Amsterdam Gastroenterology Endocrinology Metabolism (AGEM) Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
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13
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Chung MJ, Park SW, Lee KJ, Park DH, Koh DH, Lee J, Lee HS, Park JY, Bang S, Min S, Park JH, Kim SJ, Park CH. Clinical impact of pancreatic steatosis measured by CT on the risk of post-ERCP pancreatitis: a multicenter prospective trial. Gastrointest Endosc 2024; 99:214-223.e4. [PMID: 37598866 DOI: 10.1016/j.gie.2023.08.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Revised: 08/09/2023] [Accepted: 08/13/2023] [Indexed: 08/22/2023]
Abstract
BACKGROUND AND AIMS Pancreatic steatosis (PS) may be a risk factor for acute pancreatitis. Whether it is also a risk factor for post-ERCP pancreatitis (PEP) has not been evaluated. This study aimed to determine the impact of PS on PEP development. METHODS This multicenter prospective trial enrolled 786 consecutive patients who underwent contrast-enhanced abdominal CT and subsequent first-time ERCP. PS was evaluated based on pancreatic attenuation on unenhanced CT images. The risk of PS for the development of PEP was evaluated using a logistic regression model. RESULTS Of 527 patients included in the study, 157 (29.8%) had PS and 370 (70.2%) did not. At 24 hours after ERCP, there was a significant difference in the PEP identified in 22 patients (14.0%) in the PS group and 23 patients (6.2%) in the "no PS" (NPS) group (P = .017). Diabetes and hypertension were more common in the PS group than in the NPS group; no differences in dyslipidemia were found. Patients with PS had a higher risk for the development of PEP than those with NPS (odds ratio, 2.09; 95% confidence interval, 1.08-4.03). No other variables were identified as risk factors for PEP. CONCLUSIONS PS is a significant risk factor for PEP for which preventive measures should be considered. Standardized measurement protocols to assess PS by CT are needed. (Clinical trial registration number: KCT0006068.).
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Affiliation(s)
- Moon Jae Chung
- Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Se Woo Park
- Division of Gastroenterology, Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Republic of Korea
| | - Kyong Joo Lee
- Division of Gastroenterology, Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Republic of Korea
| | - Da Hae Park
- Division of Gastroenterology, Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Republic of Korea
| | - Dong Hee Koh
- Division of Gastroenterology, Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Republic of Korea
| | - Jin Lee
- Division of Gastroenterology, Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Republic of Korea
| | - Hee Seung Lee
- Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jeong Youp Park
- Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Seungmin Bang
- Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Seonjeong Min
- Department of Radiology, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Republic of Korea
| | - Ji Hoon Park
- Division of Gastroenterology, Department of Internal Medicine, CHA Ilsan Medical Center, CHA University, Goyang, Republic of Korea
| | - So Jeong Kim
- Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Chan Hyuk Park
- Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Republic of Korea
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14
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Pagkali A, Makris A, Brofidi K, Agouridis AP, Filippatos TD. Pathophysiological Mechanisms and Clinical Associations of Non-Alcoholic Fatty Pancreas Disease. Diabetes Metab Syndr Obes 2024; 17:283-294. [PMID: 38283640 PMCID: PMC10813232 DOI: 10.2147/dmso.s397643] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Accepted: 12/29/2023] [Indexed: 01/30/2024] Open
Abstract
Non-Alcoholic Fatty Pancreas disease (NAFPD), characterized by fat accumulation in pancreatic tissue, is an emerging clinical entity. However, the clinical associations, the underlying molecular drivers, and the pathophysiological mechanisms of NAFPD have not yet been characterized in detail. The NAFPD spectrum not only includes infiltration and accumulation of fat within and between pancreatic cells but also involves several inflammatory processes, dysregulation of physiological metabolic pathways, and hormonal defects. A deeper understanding of the underlying molecular mechanisms is key to correlate NAFPD with clinical entities including non-alcoholic fatty liver disease, metabolic syndrome, diabetes mellitus, atherosclerosis, as well as pancreatic cancer and pancreatitis. The aim of this review is to examine the pathophysiological mechanisms of NAFPD and to assess the possible causative/predictive risk factors of NAFPD-related clinical syndromes.
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Affiliation(s)
- Antonia Pagkali
- School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Anastasios Makris
- School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Kalliopi Brofidi
- Department of Internal Medicine, School of Medicine, University of Crete, Heraklion, Greece
| | - Aris P Agouridis
- School of Medicine, European University Cyprus, Nicosia, Cyprus
- Department of Internal Medicine, German Oncology Center, Limassol, Cyprus
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15
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Lipp M, Tarján D, Lee J, Zolcsák Á, Szalai E, Teutsch B, Faluhelyi N, Erőss B, Hegyi P, Mikó A. Fatty Pancreas Is a Risk Factor for Pancreatic Cancer: A Systematic Review and Meta-Analysis of 2956 Patients. Cancers (Basel) 2023; 15:4876. [PMID: 37835570 PMCID: PMC10571813 DOI: 10.3390/cancers15194876] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Revised: 09/29/2023] [Accepted: 10/03/2023] [Indexed: 10/15/2023] Open
Abstract
Pancreatic cancer (PC) is one of the most lethal cancers worldwide. Recently, fatty pancreas (FP) has been studied thoroughly, and although its relationship to PC is not fully understood, FP is suspected to contribute to the development of PC. We aimed to assess the association between PC and FP by conducting a systematic review and meta-analysis. We systematically searched three databases, MEDLINE, Embase, and CENTRAL, on 21 October 2022. Case-control and cross-sectional studies reporting on patients where the intra-pancreatic fat deposition was determined by modern radiology or histology were included. As main outcome parameters, FP in patients with and without PC and PC in patients with and without FP were measured. Proportion and odds ratio (OR) with a 95% confidence interval (CI) were used for effect size measure. PC among patients with FP was 32% (OR 1.32; 95% CI 0.42-4.16). However, the probability of having FP among patients with PC was more than six times higher (OR 6.13; 95% CI 2.61-14.42) than in patients without PC, whereas the proportion of FP among patients with PC was 0.62 (95% CI 0.42-0.79). Patients identified with FP are at risk of developing PC. Proper screening and follow-up of patients with FP may be recommended.
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Affiliation(s)
- Mónika Lipp
- Institute of Pancreatic Diseases, Semmelweis University, 1083 Budapest, Hungary; (M.L.); (D.T.); (B.E.); (P.H.)
- Centre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary; (J.L.); (Á.Z.); (E.S.); (B.T.); (N.F.)
- Institute for Translational Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary
| | - Dorottya Tarján
- Institute of Pancreatic Diseases, Semmelweis University, 1083 Budapest, Hungary; (M.L.); (D.T.); (B.E.); (P.H.)
- Centre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary; (J.L.); (Á.Z.); (E.S.); (B.T.); (N.F.)
| | - Jimin Lee
- Centre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary; (J.L.); (Á.Z.); (E.S.); (B.T.); (N.F.)
- Medical School, Semmelweis University, 1085 Budapest, Hungary
| | - Ádám Zolcsák
- Centre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary; (J.L.); (Á.Z.); (E.S.); (B.T.); (N.F.)
- Department of Biophysics and Radiation Biology, Semmelweis University, 1094 Budapest, Hungary
| | - Eszter Szalai
- Centre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary; (J.L.); (Á.Z.); (E.S.); (B.T.); (N.F.)
- Department of Restorative Dentistry and Endodontics, Semmelweis University, 1088 Budapest, Hungary
| | - Brigitta Teutsch
- Centre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary; (J.L.); (Á.Z.); (E.S.); (B.T.); (N.F.)
- Institute for Translational Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary
| | - Nándor Faluhelyi
- Centre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary; (J.L.); (Á.Z.); (E.S.); (B.T.); (N.F.)
- Department of Medical Imaging, Medical School, University of Pécs, 7624 Pécs, Hungary
| | - Bálint Erőss
- Institute of Pancreatic Diseases, Semmelweis University, 1083 Budapest, Hungary; (M.L.); (D.T.); (B.E.); (P.H.)
- Centre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary; (J.L.); (Á.Z.); (E.S.); (B.T.); (N.F.)
- Institute for Translational Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary
| | - Péter Hegyi
- Institute of Pancreatic Diseases, Semmelweis University, 1083 Budapest, Hungary; (M.L.); (D.T.); (B.E.); (P.H.)
- Centre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary; (J.L.); (Á.Z.); (E.S.); (B.T.); (N.F.)
- Institute for Translational Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary
- Translational Pancreatology Research Group, Interdisciplinary Centre of Excellence for Research Development and Innovation, University of Szeged, 6725 Szeged, Hungary
| | - Alexandra Mikó
- Centre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary; (J.L.); (Á.Z.); (E.S.); (B.T.); (N.F.)
- Institute for Translational Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary
- Department of Medical Genetics, Medical School, University of Pécs, 7624 Pécs, Hungary
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16
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Janssens LP, Takahashi H, Nagayama H, Nugen F, Bamlet WR, Oberg AL, Fuemmeler E, Goenka AH, Erickson BJ, Takahashi N, Majumder S. Artificial intelligence assisted whole organ pancreatic fat estimation on magnetic resonance imaging and correlation with pancreas attenuation on computed tomography. Pancreatology 2023; 23:556-562. [PMID: 37193618 DOI: 10.1016/j.pan.2023.04.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Revised: 04/18/2023] [Accepted: 04/20/2023] [Indexed: 05/18/2023]
Abstract
BACKGROUND Fatty pancreas is associated with inflammatory and neoplastic pancreatic diseases. Magnetic resonance imaging (MRI) is the diagnostic modality of choice for measuring pancreatic fat. Measurements typically use regions of interest limited by sampling and variability. We have previously described an artificial intelligence (AI)-aided approach for whole pancreas fat estimation on computed tomography (CT). In this study, we aimed to assess the correlation between whole pancreas MRI proton-density fat fraction (MR-PDFF) and CT attenuation. METHODS We identified patients without pancreatic disease who underwent both MRI and CT between January 1, 2015 and June 1, 2020. 158 paired MRI and CT scans were available for pancreas segmentation using an iteratively trained convolutional neural network (CNN) with manual correction. Boxplots were generated to visualize slice-by-slice variability in 2D-axial slice MR-PDFF. Correlation between whole pancreas MR-PDFF and age, BMI, hepatic fat and pancreas CT-Hounsfield Unit (CT-HU) was assessed. RESULTS Mean pancreatic MR-PDFF showed a strong inverse correlation (Spearman -0.755) with mean CT-HU. MR-PDFF was higher in males (25.22 vs 20.87; p = 0.0015) and in subjects with diabetes mellitus (25.95 vs 22.17; p = 0.0324), and was positively correlated with age and BMI. The pancreatic 2D-axial slice-to-slice MR-PDFF variability increased with increasing mean whole pancreas MR-PDFF (Spearman 0.51; p < 0.0001). CONCLUSION Our study demonstrates a strong inverse correlation between whole pancreas MR-PDFF and CT-HU, indicating that both imaging modalities can be used to assess pancreatic fat. 2D-axial pancreas MR-PDFF is variable across slices, underscoring the need for AI-aided whole-organ measurements for objective and reproducible estimation of pancreatic fat.
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Affiliation(s)
- Laurens P Janssens
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | | | | | - Fred Nugen
- Department of Radiology, Mayo Clinic, Rochester, MN, USA
| | - William R Bamlet
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA
| | - Ann L Oberg
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA
| | - Eric Fuemmeler
- Department of Radiology, Mayo Clinic, Rochester, MN, USA
| | - Ajit H Goenka
- Department of Radiology, Mayo Clinic, Rochester, MN, USA
| | | | | | - Shounak Majumder
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
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17
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Otsuka N, Shimizu K, Taniai M, Tokushige K. Risk factors for fatty pancreas and effects of fatty infiltration on pancreatic cancer. Front Physiol 2023; 14:1243983. [PMID: 37664430 PMCID: PMC10470060 DOI: 10.3389/fphys.2023.1243983] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Accepted: 07/25/2023] [Indexed: 09/05/2023] Open
Abstract
Objective: This study clarified the risk factors and pathophysiology of pancreatic cancer by examining the factors associated with fatty pancreas. Methods: The degree of fatty pancreas, background factors, and incidence of pancreatic cancer were examined among nonalcoholic fatty liver disease (NAFLD) patients (n = 281) and intraductal papillary mucinous neoplasm (IPMN) patients with a family history of pancreatic cancer (n = 38). The presence of fatty pancreas was confirmed by the pancreatic CT value/splenic CT value ratio (P/S ratio). Immunohistochemical staining was performed on 10 cases with fatty pancreas, confirmed via postoperative pathology. Results: Fatty pancreas occurred in 126 patients (44.8%) in the NAFLD group who were older (p = 0.0002) and more likely to have hypertension (p < 0.0001). The IPMN group had 18 patients (47.4%) with fatty pancreas, included more men than women (p = 0.0056), and was more likely to have patients with hypertension (p = 0.0010). On histological examination, a significant infiltration of adipocytes into the acini from the pancreatic interstitium induced atrophy of the pancreatic parenchyma, and both M1 and M2 macrophages were detected in the area where adipocytes invaded the pancreatic parenchyma. Accumulation of p62 and increased positive staining of NQO1 molecules related to autophagy dysfunction were detected in pancreatic acinar cells in the fatty area, acinar-ductal metaplasia, and pancreatic cancer cells. The rate of p62-positive cell area and that of NQO1-positive cell area were significantly higher in the fatty pancreatic region than those in the control lesion (pancreatic region with few adipocyte infiltration). Furthermore, the rate of p62-positive cell area or that of NQO1-positive cell area showed strong positive correlations with the rate of fatty pancreatic lesion. These results suggest that adipocyte invasion into the pancreatic parenthyme induced macrophage infiltration and autophagy substrate p62 accumulation. High levels of NQO1 expression in the fatty area may be dependent on p62 accumulation. Conclusion: Hypertension was a significant risk factor for fatty pancreas in patients with NAFLD and IPMN. In fatty pancreas, fatty infiltration into the pancreatic parenchyme might induce autophagy dysfunction, resulting in activation of antioxidant proteins NQO1. Thus, patients with fatty pancreas require careful follow-up.
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Affiliation(s)
- Nao Otsuka
- Department of Internal Medicine, Institute of Gastroenterology, Tokyo Women’s Medical University, Tokyo, Japan
| | - Kyoko Shimizu
- Department of Internal Medicine, Institute of Gastroenterology, Tokyo Women’s Medical University, Tokyo, Japan
- Shinjuku Mitsui Building Clinic, Tokyo, Japan
| | - Makiko Taniai
- Department of Internal Medicine, Institute of Gastroenterology, Tokyo Women’s Medical University, Tokyo, Japan
| | - Katsutoshi Tokushige
- Department of Internal Medicine, Institute of Gastroenterology, Tokyo Women’s Medical University, Tokyo, Japan
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18
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Andrade LJDO, Oliveira LMD, Bittencourt AMV, Baptista GM, Oliveira GCMD. ASSOCIATION BETWEEN NONALCOHOLIC FATTY PANCREATIC DISEASE AND TRIGLYCERIDE/GLUCOSE INDEX. ARQUIVOS DE GASTROENTEROLOGIA 2023; 60:345-349. [PMID: 37792764 DOI: 10.1590/s0004-2803.230302023-44] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Accepted: 05/21/2023] [Indexed: 10/06/2023]
Abstract
•Non-alcoholic fatty pancreatic disease is associated with insulin resistance. •The triglyceride-glucose index has been used as a reliable marker for the diagnosis of insulin resistance. •The triglyceride-glucose index correlates positively with the degree of non-alcoholic fatty pancreatic disease. Background - Nonalcoholic fatty pancreatic disease (NAFPD) is an increase of fat in the pancreas, and has an important association with insulin resistance (IR) and type 2 diabetes mellitus. Research has confirmed that the triglyceridemia/glycemia (TyG) index determines IR as much as does the hyperinsulinemic-euglycemic clamp assessment as the homeostasis model testing of IR (HOMA-IR). Objective - To eva-luate the association between degree of NAFPD and TyG index. Methods - In 72 patients undergoing ultrasound of abdomen with a diagnosis of NAFPD, insulin, glucose, and triglycerides levels were evaluated. The HOMA-IR and TyG indexes were used as a reference for IR. The degrees of NAFPD and the TyG index were presented through the receiver operating characteristics (ROC) curves in order to evaluate the association between different degrees of NAFPD, and the correlation of NAFPD with HOMA-IR was also evaluated. Results - There was a statistically significant correlation between the degree of NAFPD and the TyG index. The AUROC curve for the TyG index for predicting the degree of NADPD was 0.855 (0.840-0.865). The intensity-adjusted probabilities of the degree of NAFPD were more strongly associated with TyG values when compared with HOMA-IR. Conclusion - In this study the TyG index correlated positively with the degree of NAFPD, performing better than HOMA-IR.
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Petrov MS. Fatty change of the pancreas: the Pandora's box of pancreatology. Lancet Gastroenterol Hepatol 2023; 8:671-682. [PMID: 37094599 DOI: 10.1016/s2468-1253(23)00064-x] [Citation(s) in RCA: 39] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Revised: 02/12/2023] [Accepted: 02/14/2023] [Indexed: 04/26/2023]
Abstract
Prevention of common diseases of the pancreas or interception of their progression is as attractive in theory as it is elusive in practice. The fundamental challenge has been an incomplete understanding of targets coupled with a multitude of intertwined factors that are associated with the development of pancreatic diseases. Evidence over the past decade has shown unique morphological features, distinctive biomarkers, and complex relationships of intrapancreatic fat deposition. Fatty change of the pancreas has also been shown to affect at least 16% of the global population. This knowledge has solidified the pivotal role of fatty change of the pancreas in acute pancreatitis, chronic pancreatitis, pancreatic cancer, and diabetes. The pancreatic diseases originating from intrapancreatic fat (PANDORA) hypothesis advanced in this Personal View cuts across traditional disciplinary boundaries with a view to tackling these diseases. New holistic understanding of pancreatic diseases is well positioned to propel pancreatology through lasting research breakthroughs and clinical advances.
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Affiliation(s)
- Maxim S Petrov
- School of Medicine, University of Auckland, Auckland, New Zealand.
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20
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Mukherjee S, Maheshwari D, Pal R, Sachdeva N. Pancreatic fat in type 2 diabetes: Causal or coincidental? World J Meta-Anal 2023; 11:68-78. [DOI: 10.13105/wjma.v11.i3.68] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2022] [Revised: 12/27/2022] [Accepted: 02/15/2023] [Indexed: 03/01/2023] Open
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Yi J, Xu F, Li T, Liang B, Li S, Feng Q, Long L. Quantitative study of 3T MRI qDixon-WIP applied in pancreatic fat infiltration in patients with type 2 diabetes mellitus. Front Endocrinol (Lausanne) 2023; 14:1140111. [PMID: 36875489 PMCID: PMC9981945 DOI: 10.3389/fendo.2023.1140111] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2023] [Accepted: 02/02/2023] [Indexed: 02/19/2023] Open
Abstract
OBJECTIVE To investigate the application value of 3T MRI qDixon-WIP technique in the quantitative measurement of pancreatic fat content in patients with type 2 diabetes mellitus (T2DM). METHODS The 3T MRI qDixon-WIP sequence was used to scan the livers and the pancreas of 47 T2DM patients (experimental group) and 48 healthy volunteers (control group). Pancreatic fat fraction (PFF), hepatic fat fraction (HFF), Body mass index (BMI) ratio of pancreatic volume to body surface area (PVI) were measured. Total cholesterol (TC), subcutaneous fat area (SA), triglyceride (TG), abdominal visceral fat area (VA), high density lipoprotein (HDL-c), fasting blood glucose (FPC) and low-density lipoprotein (LDL-c) were collected. The relationship between the experimental group and the control group and between PFF and other indicators was compared. The differences of PFF between the control group and different disease course subgroups were also explored. RESULTS There was no significant difference in BMI between the experimental group and the control group (P=0.231). PVI, SA, VA, PFF and HFF had statistical differences (P<0.05). In the experimental group, PFF was highly positively correlated with HFF (r=0.964, P<0.001), it was moderately positively correlated with TG and abdominal fat area (r=0.676, 0.591, P<0.001), and it was weakly positively correlated with subcutaneous fat area (r=0.321, P=0.033). And it had no correlation with FPC, PVI, HDL-c, TC and LDL-c (P>0.05). There were statistical differences in PFF between the control group and the patients with different course of T2DM (P<0.05). There was no significant difference in PFF between T2DM patients with a disease course ≤1 year and those with a disease course <5 years (P>0.05). There were significant differences in PFF between the groups with a disease course of 1-5 years and those with a disease course of more than 5 years (P<0.001). CONCLUSION PVI of T2DM patients is lower than normal, but SA, VA, PFF, HFF are higher than normal. The degree of pancreatic fat accumulation in T2DM patients with long disease course was higher than that in patients with short disease course. The qDixon-WIP sequence can provide an important reference for clinical quantitative evaluation of fat content in T2DM patients.
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Affiliation(s)
- Jixing Yi
- Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, China
- Department of Radiology, Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou Worker’s Hospital Guangxi Zhuang Autonomous Region, Liuzhou, China
| | - Fengming Xu
- Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, China
| | - Tao Li
- Department of Radiology, Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou Worker’s Hospital Guangxi Zhuang Autonomous Region, Liuzhou, China
| | - Bumin Liang
- School of International Education, Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, China
| | - Shu Li
- Department of Radiology, Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou Worker’s Hospital Guangxi Zhuang Autonomous Region, Liuzhou, China
| | - Qing Feng
- Department of Radiology, Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou Worker’s Hospital Guangxi Zhuang Autonomous Region, Liuzhou, China
| | - Liling Long
- Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, China
- *Correspondence: Liling Long,
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22
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Rugivarodom M, Geeratragool T, Pausawasdi N, Charatcharoenwitthaya P. Fatty Pancreas: Linking Pancreas Pathophysiology to Nonalcoholic Fatty Liver Disease. J Clin Transl Hepatol 2022; 10:1229-1239. [PMID: 36381092 PMCID: PMC9634764 DOI: 10.14218/jcth.2022.00085] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 06/05/2022] [Accepted: 06/27/2022] [Indexed: 12/04/2022] Open
Abstract
Currently, scientific interest has focused on fat accumulation outside of subcutaneous adipose tissue. As various imaging modalities are available to quantify fat accumulation in particular organs, fatty pancreas has become an important area of research over the last decade. The pancreas has an essential role in regulating glucose metabolism and insulin secretion by responding to changes in nutrients under various metabolic circumstances. Mounting evidence has revealed that fatty pancreas is linked to impaired β-cell function and affects insulin secretion with metabolic consequences of impaired glucose metabolism, type 2 diabetes, and metabolic syndrome. It has been shown that there is a connection between fatty pancreas and the presence and severity of nonalcoholic fatty liver disease (NAFLD), which has become the predominant cause of chronic liver disease worldwide. Therefore, it is necessary to better understand the pathogenic mechanisms of fat accumulation in the pancreas and its relationship with NAFLD. This review summarizes the epidemiology, diagnosis, risk factors, and metabolic consequences of fatty pancreas and discusses its pathophysiology links to NAFLD.
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Affiliation(s)
| | | | | | - Phunchai Charatcharoenwitthaya
- Correspondence to: Phunchai Charatcharoenwitthaya, Division of Gastroenterology, Medicine Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Wang-Lang Road, Bangkok 10700, Thailand. ORCID: https://orcid.org/0000-0002-8334-0267. Tel: +66-2-4197282, Fax: +66-2-4115013, E-mail:
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23
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Golbasi H, Bayraktar B, Golbasi C, Omeroglu I, Adiyaman D, Sever B, Ekin A. Can sonographic imaging of the fetal pancreas predict perinatal outcomes in gestational diabetes mellitus? J Perinat Med 2022; 50:1189-1197. [PMID: 35607725 DOI: 10.1515/jpm-2022-0050] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2022] [Accepted: 04/27/2022] [Indexed: 11/15/2022]
Abstract
OBJECTIVES To evaluate whether fetal pancreatic echogenicity and its measurements are associated with gestational diabetes mellitus (GDM) and perinatal outcomes. METHODS A prospective cohort study was conducted with 150 pregnant women with a singleton pregnancy. The study included pregnant women between 30 and 41 weeks with or without GDM. Fetal pancreatic circumference was measured using the free-hand tracking function. The echogenicity of the fetal pancreas was compared with the echogenicity of the liver and bone (ribs, spine) and classified as Grades 1, 2 and 3. The relationship between maternal characteristics and perinatal outcomes with fetal pancreas measurements and echogenicity was evaluated. RESULTS Pregnant women with 75 GDM and 75 without GDM were included in the study. Mean fetal pancreas circumference measurements were significantly higher in pregnant women with GDM than in those without GDM (p=0.001). Hyperechogenic (Grade 3) fetal pancreas was significantly higher in pregnant women with GDM than in pregnant women without GDM, and there was a positive correlation between pancreatic echogenicity and HbA1c levels in pregnant women with GDM (r=0.631, p<0.01). There was a significant relationship between pancreatic echogenicity, measurements and adverse neonatal outcomes in pregnant women with GDM, and pancreas measurements were significantly higher in pregnant women with cesarean delivery. CONCLUSIONS Fetal pancreatic echogenicity and measurements in pregnant women with GDM can give an idea about glucose regulation and adverse perinatal outcomes.
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Affiliation(s)
- Hakan Golbasi
- Department of Obstetrics and Gynecology Division of Perinatology, University of Health Sciences Tepecik Training and Research Hospital, Izmir, Turkey
| | - Burak Bayraktar
- Department of Obstetrics and Gynecology, University of Health Sciences Tepecik Training and Research Hospital, Izmir, Turkey
| | - Ceren Golbasi
- Department of Obstetrics and Gynecology, Izmir Tinaztepe University Faculty of Medicine, Izmir, Turkey
| | - Ibrahim Omeroglu
- Department of Obstetrics and Gynecology Division of Perinatology, University of Health Sciences Tepecik Training and Research Hospital, Izmir, Turkey
| | - Duygu Adiyaman
- Department of Obstetrics and Gynecology Division of Perinatology, University of Health Sciences Tepecik Training and Research Hospital, Izmir, Turkey
| | - Baris Sever
- Department of Obstetrics and Gynecology Division of Perinatology, University of Health Sciences Tepecik Training and Research Hospital, Izmir, Turkey
| | - Atalay Ekin
- Department of Obstetrics and Gynecology Division of Perinatology, University of Health Sciences Tepecik Training and Research Hospital, Izmir, Turkey
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Obesity and cancer-extracellular matrix, angiogenesis, and adrenergic signaling as unusual suspects linking the two diseases. Cancer Metastasis Rev 2022; 41:517-547. [PMID: 36074318 PMCID: PMC9470659 DOI: 10.1007/s10555-022-10058-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Accepted: 07/29/2022] [Indexed: 12/24/2022]
Abstract
Obesity is an established risk factor for several human cancers. Given the association between excess body weight and cancer, the increasing rates of obesity worldwide are worrisome. A variety of obesity-related factors has been implicated in cancer initiation, progression, and response to therapy. These factors include circulating nutritional factors, hormones, and cytokines, causing hyperinsulinemia, inflammation, and adipose tissue dysfunction. The impact of these conditions on cancer development and progression has been the focus of extensive literature. In this review, we concentrate on processes that can link obesity and cancer, and which provide a novel perspective: extracellular matrix remodeling, angiogenesis, and adrenergic signaling. We describe molecular mechanisms involved in these processes, which represent putative targets for intervention. Liver, pancreas, and breast cancers were chosen as exemplary disease models. In view of the expanding epidemic of obesity, a better understanding of the tumorigenic process in obese individuals might lead to more effective treatments and preventive measures.
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Clinical Significance of Pancreatic Fat in Children: A Single-Center Experience. Pancreas 2022; 51:972-975. [PMID: 36607942 DOI: 10.1097/mpa.0000000000002121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
OBJECTIVES Recently, interest in pancreatic fat has increased, and fatty pancreas is considered to be related to nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome. We aimed to evaluate the prevalence of echogenic pancreas in children and its related factors. METHODS We retrospectively analyzed the data of patients aged 5 to 18 years who had undergone abdominal sonography between January 2020 and December 2020. Patients with chronic or pancreatic diseases were excluded. RESULTS Of 102 patients, 27 (26.5%) had echogenic pancreas and 55 (53.9%) had NAFLD. Among the 55 patients with NAFLD, 18 (32.7%) had an echogenic pancreas. Patients with echogenic pancreas had significantly higher fasting glucose, low-density lipoprotein cholesterol, and triglyceride levels than those without echogenic pancreas. The proportion of NAFLD and obesity was higher in the echogenic group; however, only the proportion of obese subjects showed a significant difference. In multivariate analysis, family history of diabetes mellitus (DM) and/or dyslipidemia and presence of DM and/or dyslipidemia were factors related to the presence of echogenic pancreas. CONCLUSIONS Echogenic pancreas is relatively common in children. Echogenic pancreas, typically observed in patients with a family history of DM and/or dyslipidemia, was strongly associated with metabolic syndrome, even in the absence of fatty liver.
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Hong C, Yan Y, Su L, Chen D, Zhang C. Development of a risk-stratification scoring system for predicting risk of breast cancer based on non-alcoholic fatty liver disease, non-alcoholic fatty pancreas disease, and uric acid. Open Med (Wars) 2022; 17:619-625. [PMID: 35434374 PMCID: PMC8974397 DOI: 10.1515/med-2022-0462] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Revised: 02/15/2022] [Accepted: 02/22/2022] [Indexed: 12/24/2022] Open
Abstract
Many breast cancer patients have both non-alcoholic fatty liver disease (NAFLD) and non-alcoholic fatty pancreas disease (NAFPD). Consequently, we hypothesized that NAFPD and NAFLD were associated with breast cancer, and aimed to build a novel risk-stratification scoring system based on it. In this study, a total of 961 patients with breast cancer and 1,006 non-cancer patients were recruited. The clinical characteristics were collected and analyzed using logistic analysis. Risk factors were assessed by a risk rating system. Univariate analysis showed that body mass index, triglyceride, total cholesterol, NAFLD, NAFPD, low-density lipoprotein, and uric acid (UA) were significantly related to breast cancer. Among them, NAFLD, NAFPD, and UA were independent risk factors related to breast cancer identified by multivariate analysis. The risk assessment model was established based on these factors and demonstrated that the odds ratio sharply increased with the rising scores. Compared with the low-risk group, the odds ratio in the intermediate- and high-risk groups were 1.662 (1.380–2.001) and 3.185 (2.145–4.728), respectively. In conclusion, the risk-stratification scoring system combining NAFLD, NAFPD, and UA can accurately predict the occurrence of breast cancer.
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Affiliation(s)
- Chuntian Hong
- Department of Ultrasound, Quanzhou First Hospital Affiliated to Fujian Medical University , Quanzhou 362000 , China
| | - Yonghao Yan
- Department of Ultrasound, Quanzhou First Hospital Affiliated to Fujian Medical University , Quanzhou 362000 , China
| | - Liyang Su
- Department of Ultrasound, Quanzhou First Hospital Affiliated to Fujian Medical University , Quanzhou 362000 , China
| | - Debo Chen
- Department of Breast Surgery, Quanzhou First Hospital Affiliated to Fujian Medical University , Quanzhou 362000 , China
| | - Changqing Zhang
- Department of Gastroenterology, Quanzhou First Hospital Affiliated to Fujian Medical University , Quanzhou 362000 , China
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Bhalla S, Kuchel GA, Pandol S, Bishehsari F. Association of Pancreatic Fatty Infiltration With Age and Metabolic Syndrome Is Sex-Dependent. GASTRO HEP ADVANCES 2022; 1:344-349. [PMID: 39131675 PMCID: PMC11308813 DOI: 10.1016/j.gastha.2022.01.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Accepted: 01/25/2022] [Indexed: 08/13/2024]
Abstract
Background and Aims Fatty infiltration of the pancreas has been shown to be associated with both precancerous pancreatic lesions and pancreatic ductal adenocarcinoma. We aim to determine predictors of fatty infiltration of the pancreas in United States adults. Methods In this retrospective cohort study conducted at a large academic hospital in Chicago, Illinois, we calculated the relative fatty infiltration of the pancreas (corrected to spleen) of 265 cancer-free individuals based on their cross-sectional imaging. Demographic data and relevant laboratory results were obtained from medical records. Results We found that age was the strongest predictor of fatty infiltration of the pancreas in our series (P < .01). Fatty infiltration of the pancreas was also significantly associated with body mass index (P < .01) and hyperlipidemia (P < .05). In women, in addition to age (P < .05), elevated body mass index (P = .023), hyperlipidemia (P = .013), and fatty liver (P = .017) were predictors of fat in pancreas. We found a sex-dependent association between pancreatic fat and metabolic syndrome including fatty liver (P = .002). Conclusion Fatty infiltration of the pancreas increases by age and components of metabolic syndrome. These assertions could be sex-dependent.
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Affiliation(s)
- Sameer Bhalla
- Division of Digestive Diseases and Nutrition, Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois
| | - George A. Kuchel
- UConn Center on Aging, University of Connecticut, Farmington, Connecticut
| | - Stephen Pandol
- Division of Digestive and Liver Disease, Cedars-Sinai Medical Center, Los Angeles, California
| | - Faraz Bishehsari
- Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, Illinois
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Ensemble Convolutional Neural Network Classification for Pancreatic Steatosis Assessment in Biopsy Images. INFORMATION 2022. [DOI: 10.3390/info13040160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/10/2022] Open
Abstract
Non-alcoholic fatty pancreas disease (NAFPD) is a common and at the same time not extensively examined pathological condition that is significantly associated with obesity, metabolic syndrome, and insulin resistance. These factors can lead to the development of critical pathogens such as type-2 diabetes mellitus (T2DM), atherosclerosis, acute pancreatitis, and pancreatic cancer. Until recently, the diagnosis of NAFPD was based on noninvasive medical imaging methods and visual evaluations of microscopic histological samples. The present study focuses on the quantification of steatosis prevalence in pancreatic biopsy specimens with varying degrees of NAFPD. All quantification results are extracted using a methodology consisting of digital image processing and transfer learning in pretrained convolutional neural networks for the detection of histological fat structures. The proposed method is applied to 20 digitized histological samples, producing an 0.08% mean fat quantification error thanks to an ensemble CNN voting system and 83.3% mean Dice fat segmentation similarity compared to the semi-quantitative estimates of specialist physicians.
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Fatty Pancreas-Centered Metabolic Basis of Pancreatic Adenocarcinoma: From Obesity, Diabetes and Pancreatitis to Oncogenesis. Biomedicines 2022; 10:biomedicines10030692. [PMID: 35327494 PMCID: PMC8945032 DOI: 10.3390/biomedicines10030692] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Revised: 03/11/2022] [Accepted: 03/15/2022] [Indexed: 12/13/2022] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest types of cancer, and it is currently the third most common cause of cancer death in the U.S.A. Progress in the fight against PDAC has been hampered by an inability to detect it early in the overwhelming majority of patients, and also by the reduced oxygen levels and nutrient perfusion caused by new matrix formation through the activation of stromal cells in the context of desmoplasia. One harbinger of PDAC is excess intrapancreatic fat deposition, namely, fatty pancreas, which specifically affects the tumor macro- and microenvironment in the organ. Over half of PDAC patients have diabetes mellitus (DM) at the time of diagnosis, and fatty pancreas is associated with subsequent DM development. Moreover, there is a strong association between fatty pancreas and fatty liver through obesity, and a higher intrapancreatic fat percentage has been noted in acute pancreatitis patients with DM than in those without DM. All these findings suggest that the link between fatty pancreas and PDAC might occur through metabolic alterations, either DM-related or non-DM-related. Based on clinical, in vivo and in vitro evidence, the current review highlights the etiologies of fatty pancreas (including fatty infiltration and replacement) and the fatty pancreas-associated metabolic alterations involved in oncogenesis to provide crucial targets to prevent, detect, and/or effectively treat PDAC.
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The Coexistence of Nonalcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus. J Clin Med 2022; 11:jcm11051375. [PMID: 35268466 PMCID: PMC8910939 DOI: 10.3390/jcm11051375] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 02/28/2022] [Accepted: 03/01/2022] [Indexed: 12/12/2022] Open
Abstract
The incidence of nonalcoholic fatty liver disease (NAFLD) is growing worldwide. Epidemiological data suggest a strong relationship between NAFLD and T2DM. This is associated with common risk factors and pathogenesis, where obesity, insulin resistance and dyslipidemia play pivotal roles. Expanding knowledge on the coexistence of NAFLD and T2DM could not only protect against liver damage and glucotoxicity, but may also theoretically prevent the subsequent occurrence of other diseases, such as cancer and cardiovascular disorders, as well as influence morbidity and mortality rates. In everyday clinical practice, underestimation of this problem is still observed. NAFLD is not looked for in T2DM patients; on the contrary, diagnosis for glucose metabolism disturbances is usually not performed in patients with NAFLD. However, simple and cost-effective methods of detection of fatty liver in T2DM patients are still needed, especially in outpatient settings. The treatment of NAFLD, especially where it coexists with T2DM, consists mainly of lifestyle modification. It is also suggested that some drugs, including hypoglycemic agents, may be used to treat NAFLD. Therefore, the aim of this review is to detail current knowledge of NAFLD and T2DM comorbidity, its prevalence, common pathogenesis, diagnostic procedures, complications and treatment, with special attention to outpatient clinics.
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Prevalence of Findings in Routine Abdominal Ultrasound in Patients with Systemic Autoimmune Rheumatic Diseases and Their Impact on Therapeutic Decision Making. APPLIED SCIENCES-BASEL 2022. [DOI: 10.3390/app12020851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Patients with systemic autoimmune rheumatic diseases (SARD) often receive abdominal ultrasound examinations to screen for organ involvement; yet, the spectrum of findings and their clinical relevance are poorly understood. We conducted a retrospective chart review of inpatients from a rheumatological referral centre with an abdominal ultrasound between 1 January2006 and 31 December 2015, examining 1092 SARD patients with a total of 1695 inpatient stays. The mean age was 55.1 years (range: 17–90 years, SD: 15.8), and the mean disease duration was 6.4 years (range: 0.0–52.8 years, SD: 9.1). A total of 87.5% of the patients were female. The most frequent ultrasound findings were hepatic steatosis (in 26.8% of all patients), splenomegaly (15.2% of all patients), pancreatic lipomatosis (14.3% of all patients) and aortic sclerosis (13.9% of all patients). Based on glucocorticoid and disease-modifying antirheumatic drug use, we identified cases where immuno-modulatory medication was escalated; there was an association between therapy escalation and the findings of hepatomegaly and pleural effusion (as tested via Fisher’s exact test). In patients with several examinations during the defined time span (n = 318), we found ultrasound findings to change, especially findings of hepatomegaly, pleural effusion and splenomegaly. When justifying decisions regarding the further treatment of a patient in the discharge letter, abdominal ultrasound results were rarely discussed. Abdominal ultrasound rarely yielded disease-specific or treatment-changing results.
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Pancreatic Steatosis Is Associated with Both Metabolic Syndrome and Pancreatic Stiffness Detected by Ultrasound Elastography. Dig Dis Sci 2022; 67:293-304. [PMID: 33651254 DOI: 10.1007/s10620-021-06844-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2020] [Accepted: 01/10/2021] [Indexed: 12/16/2022]
Abstract
INTRODUCTION There is increasing evidence that pancreatic steatosis (PS) is associated with metabolic syndrome (MS). However, it is not known whether it is associated with PS grade and pancreatic stiffness, or not. We aimed to evaluate the relationship between PS and its grade detected by transabdominal ultrasound, and pancreatic stiffness determined by two-dimensional shearwave elastography (2D-SWE), whether it has clinical significance and its relationship with MS. METHODS Patients with and without PS were evaluated prospectively. RESULTS Patients with PS had higher odds ratio for MS (OR 5.49). Also, ultrasonographic grade of PS was associated with MS parameters and hepatosteatosis. Pancreatic SWE value was significantly higher in PS group and positively correlated with PS grade, liver fat, MS, number of MS criteria. DISCUSSION/CONCLUSION PS and its grade were associated with MS. In this first comprehensive PS-SWE study, we found that pancreas stiffness increased in the presence of PS, in correlation with PS grade and MS.
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Wagner R, Eckstein SS, Yamazaki H, Gerst F, Machann J, Jaghutriz BA, Schürmann A, Solimena M, Singer S, Königsrainer A, Birkenfeld AL, Häring HU, Fritsche A, Ullrich S, Heni M. Metabolic implications of pancreatic fat accumulation. Nat Rev Endocrinol 2022; 18:43-54. [PMID: 34671102 DOI: 10.1038/s41574-021-00573-3] [Citation(s) in RCA: 82] [Impact Index Per Article: 27.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/13/2021] [Indexed: 12/15/2022]
Abstract
Fat accumulation outside subcutaneous adipose tissue often has unfavourable effects on systemic metabolism. In addition to non-alcoholic fatty liver disease, which has received considerable attention, pancreatic fat has become an important area of research throughout the past 10 years. While a number of diagnostic approaches are available to quantify pancreatic fat, multi-echo Dixon MRI is currently the most developed method. Initial studies have shown associations between pancreatic fat and the metabolic syndrome, impaired glucose metabolism and type 2 diabetes mellitus. Pancreatic fat is linked to reduced insulin secretion, at least under specific circumstances such as prediabetes, low BMI and increased genetic risk of type 2 diabetes mellitus. This Review summarizes the possible causes and metabolic consequences of pancreatic fat accumulation. In addition, potential therapeutic approaches for addressing pancreatic fat accumulation are discussed.
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Affiliation(s)
- Robert Wagner
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Tübingen, Germany
- Department of Internal Medicine, Division of Diabetology, Endocrinology, and Nephrology, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Sabine S Eckstein
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Tübingen, Germany
| | - Hajime Yamazaki
- Section of Clinical Epidemiology, Department of Community Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Felicia Gerst
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Tübingen, Germany
- Department of Internal Medicine, Division of Diabetology, Endocrinology, and Nephrology, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Jürgen Machann
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Tübingen, Germany
- Section of Experimental Radiology, Department of Diagnostic and Interventional Radiology, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Benjamin Assad Jaghutriz
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Tübingen, Germany
- Department of Internal Medicine, Division of Diabetology, Endocrinology, and Nephrology, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Annette Schürmann
- German Center for Diabetes Research (DZD), Tübingen, Germany
- Department of Experimental Diabetology, German Institute of Human Nutrition (DIfE), Potsdam-Rehbrücke, Germany
- Institute of Nutritional Science, University of Potsdam, Potsdam, Germany
| | - Michele Solimena
- German Center for Diabetes Research (DZD), Tübingen, Germany
- Molecular Diabetology, University Hospital and Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany
- Paul Langerhans Institute Dresden (PLID), Helmholtz Center Munich, University Hospital and Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany
| | - Stephan Singer
- Institute of Pathology, University of Tübingen, Tübingen, Germany
| | - Alfred Königsrainer
- Department of General, Visceral, and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany
| | - Andreas L Birkenfeld
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Tübingen, Germany
- Department of Internal Medicine, Division of Diabetology, Endocrinology, and Nephrology, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Hans-Ulrich Häring
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Tübingen, Germany
- Department of Internal Medicine, Division of Diabetology, Endocrinology, and Nephrology, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Andreas Fritsche
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Tübingen, Germany
- Department of Internal Medicine, Division of Diabetology, Endocrinology, and Nephrology, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Susanne Ullrich
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Tübingen, Germany
- Department of Internal Medicine, Division of Diabetology, Endocrinology, and Nephrology, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Martin Heni
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany.
- German Center for Diabetes Research (DZD), Tübingen, Germany.
- Department of Internal Medicine, Division of Diabetology, Endocrinology, and Nephrology, Eberhard Karls University Tübingen, Tübingen, Germany.
- Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital Tübingen, Tübingen, Germany.
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Filippatos TD, Alexakis K, Mavrikaki V, Mikhailidis DP. Nonalcoholic Fatty Pancreas Disease: Role in Metabolic Syndrome, "Prediabetes," Diabetes and Atherosclerosis. Dig Dis Sci 2022; 67:26-41. [PMID: 33469809 DOI: 10.1007/s10620-021-06824-7] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Accepted: 01/05/2021] [Indexed: 02/06/2023]
Abstract
Fat accumulation in the pancreas associated with obesity and the metabolic syndrome (MetS) has been defined as "non-alcoholic fatty pancreas disease" (NAFPD). The aim of this review is to describe the association of NAFPD with obesity, MetS, type 2 diabetes mellitus (T2DM) and atherosclerosis and also increase awareness regarding NAFPD. Various methods are used for the detection and quantification of pancreatic fat accumulation that may play a significant role in the differences that have been observed in the prevalence of NAFPD. Endoscopic ultrasound provides detailed images of the pancreas and its use is expected to increase in the future. Obesity and MetS have been recognized as NAFPD risk factors. NAFPD is strongly associated with non-alcoholic fatty liver disease (NAFLD) and it seems that the presence of both may be related with aggravation of NAFLD. A role of NAFPD in the development of "prediabetes" and T2DM has also been suggested by most human studies. Accumulation of fat in pancreatic tissue possibly initiates a vicious cycle of beta-cell deterioration and further pancreatic fat accumulation. Additionally, some evidence indicates a correlation between NAFPD and atherosclerotic markers (e.g., carotid intima-media thickness). Weight loss and bariatric surgery decreases pancreatic triglyceride content but pharmacologic treatments for NAFPD have not been evaluated in specifically designed studies. Hence, NAFPD is a marker of local fat accumulation possibly associated with beta-cell function impairment, carbohydrate metabolism disorders and atherosclerosis.
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Affiliation(s)
- T D Filippatos
- Metabolic Diseases Research Unit, Internal Medicine Laboratory, School of Medicine, Faculty of Medicine, University of Crete, P.O. Box 2208, Heraklion, Crete, Greece.
| | - K Alexakis
- Metabolic Diseases Research Unit, Internal Medicine Laboratory, School of Medicine, Faculty of Medicine, University of Crete, P.O. Box 2208, Heraklion, Crete, Greece
| | - V Mavrikaki
- Metabolic Diseases Research Unit, Internal Medicine Laboratory, School of Medicine, Faculty of Medicine, University of Crete, P.O. Box 2208, Heraklion, Crete, Greece
| | - D P Mikhailidis
- Department of Clinical Biochemistry, Royal Free Campus, University College London Medical School, University College London (UCL), London, NW3 2QG, UK.,Mohammed Bin Rashid University (MBRU) of Medicine and Health Sciences, Dubai, United Arab Emirates
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Berger Z, Orellana F, Cocio R, Torres F, Simian D, Araneda G, Toledo P. Pancreatic steatosis: A frequent finding in a Chilean population. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2021; 88:118-124. [PMID: 34974993 DOI: 10.1016/j.rgmxen.2021.12.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Accepted: 06/02/2021] [Indexed: 12/13/2022]
Abstract
INTRODUCTION AND AIMS Pancreatic steatosis is an incidental radiologic finding in asymptomatic patients, and its clinical importance is unclear. Primary aim: to study the prevalence of pancreatic steatosis (PS) in consecutive patients registered at our hospital, that underwent computed axial tomography (CAT) scanning of the abdomen and pelvis, excluding known pancreatic diseases. Secondary aim: to review the association of PS with the demographic and clinical data of the patients, as well as with hepatic steatosis (HS). MATERIALS AND METHODS An observational study was conducted on adult patients that had CAT scans of the abdomen and pelvis. DEFINITIONS a) tissue density was measured in Hounsfield units (HU) in five 1 cm2 areas of the pancreas, three areas of the spleen, and in segments VI and VII of the liver; b) fatty pancreas: a difference < -10 HU between the mean pancreas and mean spleen densities; and c) fatty liver: density < 40 HU. We registered the epidemiologic and laboratory data of the patients. The association of those factors with the presence of PS was analyzed using SPSS version 24.0 software, and statistical significance was set at a p < 0.05. RESULTS Of the 203 patients, PS was found in 61 (30%). The patients with PS were significantly older and had a higher body mass index. We found no significant association with the rest of the parameters studied, nor with HS (55 patients). None of the patients had symptoms attributable to a disease of the exocrine pancreas. CONCLUSIONS Fatty infiltration of the pancreas is a frequent finding in CAT scans, and its clinical importance is unclear. Aging of the population and the increase in obesity underline the need for future studies on PS.
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Affiliation(s)
- Z Berger
- Sección de Gastroenterología, Departamento de Medicina, Hospital Clínico Universidad de Chile, Santiago, Chile.
| | - F Orellana
- Sección de Gastroenterología, Departamento de Medicina, Hospital Clínico Universidad de Chile, Santiago, Chile
| | - R Cocio
- Departamento de Imagenología, Hospital Clínico Universidad de Chile, Santiago, Chile
| | - F Torres
- Sección de Gastroenterología, Departamento de Medicina, Hospital Clínico Universidad de Chile, Santiago, Chile
| | - D Simian
- Sección de Gastroenterología, Departamento de Medicina, Hospital Clínico Universidad de Chile, Santiago, Chile
| | - G Araneda
- Sección de Gastroenterología, Departamento de Medicina, Hospital Clínico Universidad de Chile, Santiago, Chile
| | - P Toledo
- Sección de Gastroenterología, Departamento de Medicina, Hospital Clínico Universidad de Chile, Santiago, Chile
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Kawamura A, Takakura K, Torisu Y, Kinoshita Y, Tomita Y, Nakano M, Yamauchi T, Suka M, Sumiyama K, Koido S, Saruta M. Impact of qualitative endoscopic ultrasonography on fatty pancreas at a referral medical center. JGH Open 2021; 6:44-49. [PMID: 35071787 PMCID: PMC8762627 DOI: 10.1002/jgh3.12692] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Revised: 10/13/2021] [Accepted: 11/28/2021] [Indexed: 11/24/2022]
Abstract
Background Taking advantage of the current advances in diagnostic imaging modalities, including endoscopic ultrasonography (EUS), and due to the increased attention to ectopic fat accumulation in the pancreas following the rising trend of metabolic syndrome, we qualitatively assessed the clinical implication of pancreatic steatosis by EUS in this study. Methods The study included 243 patients that were divided into four groups. The correlation between the average echogenicity of the pancreas and that of the control organs and the key clinical data of all study patients were collectively analyzed. The cut‐off point of the pancreas‐control (PC) ratio in EUS and liver‐control (LC) ratio on abdominal ultrasound were determined from the population distribution and the obtained median values. Results With the cut‐off point of 1.30 for the PC ratio and 1.20 for the LC ratio, sex, the Brinkman index, habitual alcohol drinkers, and fatty pancreas were significant factors. The associations between each relevant factor in fatty pancreas, metabolic syndrome in the fatty liver group, and age in the pancreatic cancer group were all significant in the analysis. In addition, we investigated whether the PC ratio differed according to age and staging in pancreatic cancer patients. Interestingly, the PC ratio was lower in the advanced stage group than in the early‐stage group. Conclusion Our results suggest that, irrespective of the degree, ectopic fat infiltration in the pancreas could be a specific clinical phenotype of serious pancreatic diseases, including pancreatic cancer, especially in high‐risk patients.
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Affiliation(s)
- Atsushi Kawamura
- Division of Gastroenterology and Hepatology, Department of Internal Medicine The Jikei University School of Medicine Tokyo Japan
| | - Kazuki Takakura
- Division of Gastroenterology and Hepatology, Department of Internal Medicine The Jikei University School of Medicine Tokyo Japan
- UnMed Clinic Motomachi Kanagawa Japan
| | - Yuichi Torisu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine The Jikei University School of Medicine Tokyo Japan
| | - Yuji Kinoshita
- Division of Gastroenterology and Hepatology, Department of Internal Medicine The Jikei University School of Medicine Tokyo Japan
| | - Yoichi Tomita
- Division of Gastroenterology and Hepatology, Department of Internal Medicine The Jikei University School of Medicine Tokyo Japan
| | - Masanori Nakano
- Division of Gastroenterology and Hepatology, Department of Internal Medicine The Jikei University School of Medicine Tokyo Japan
| | - Takashi Yamauchi
- Department of Public Health and Environmental Medicine The Jikei University School of Medicine Tokyo Japan
| | - Machi Suka
- Department of Public Health and Environmental Medicine The Jikei University School of Medicine Tokyo Japan
| | - Kazuki Sumiyama
- Department of Endoscopy The Jikei University School of Medicine Tokyo Japan
| | - Shigeo Koido
- Division of Gastroenterology and Hepatology, Department of Internal Medicine The Jikei University School of Medicine Tokyo Japan
| | - Masayuki Saruta
- Division of Gastroenterology and Hepatology, Department of Internal Medicine The Jikei University School of Medicine Tokyo Japan
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Filippatos TD. Non-Alcoholic Fatty Pancreas Disease: A Diagnosis of Increasing Importance. Angiology 2021; 73:495-496. [PMID: 34747669 DOI: 10.1177/00033197211053902] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Affiliation(s)
- Theodosios D Filippatos
- Metabolic Diseases Research Unit, Internal Medicine, Laboratory, School of Medicine, 37777University of Crete, Heraklion, Greece
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Uchida C, Mizukami H, Hara Y, Saito T, Umetsu S, Igawa A, Osonoi S, Kudoh K, Yamamoto Y, Yamamoto H, Yagihashi S, Hakamada K. Diabetes in Humans Activates Pancreatic Stellate Cells via RAGE in Pancreatic Ductal Adenocarcinoma. Int J Mol Sci 2021; 22:11716. [PMID: 34769147 PMCID: PMC8584151 DOI: 10.3390/ijms222111716] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Revised: 10/13/2021] [Accepted: 10/25/2021] [Indexed: 01/02/2023] Open
Abstract
Pancreatic stellate cells (PSCs) mainly consist of cancer-associating fibroblasts in pancreatic ductal adenocarcinoma (PDAC). The receptor for advanced glycation end products (RAGE) is implicated in the pathophysiology of diabetic complications. Here, we studied the implication of RAGE in PSC activation in PDAC. The activation of cultured mouse PSCs was evaluated by qPCR. The induction of epithelial mesenchymal transition (EMT) in PDAC cell lines was assessed under stimulation with culture supernatant from activated PSCs. A total of 155 surgically resected PDAC subjects (83 nondiabetic, 18 with ≦3-years and 54 with >3-years history of diabetes) were clinicopathologically evaluated. A high-fat diet increased the expression of activated markers in cultured PSCs, which was abrogated by RAGE deletion. Culture supernatant from activated PSCs facilitated EMT of PDAC cells with elevation of TGF-β and IL-6, but not from RAGE-deleted PSCs. Diabetic subjects complicated with metabolic syndrome, divided by cluster analysis, showed higher PSC activation and RAGE expression. In such groups, PDAC cells exhibited an EMT nature. The complication of metabolic syndrome with diabetes significantly worsened disease-free survival of PDAC subjects. Thus, RAGE in PSCs can be viewed as a new promoter and a future therapeutic target of PDAC in diabetic subjects with metabolic syndrome.
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Affiliation(s)
- Chiaki Uchida
- Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan; (C.U.); (Y.H.); (A.I.); (S.O.); (K.K.); (S.Y.)
- Department of Gasrtroenterological and Pediatric Surgery, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan; (T.S.); (S.U.); (K.H.)
| | - Hiroki Mizukami
- Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan; (C.U.); (Y.H.); (A.I.); (S.O.); (K.K.); (S.Y.)
| | - Yutaro Hara
- Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan; (C.U.); (Y.H.); (A.I.); (S.O.); (K.K.); (S.Y.)
- Department of Gasrtroenterological and Pediatric Surgery, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan; (T.S.); (S.U.); (K.H.)
| | - Takeshi Saito
- Department of Gasrtroenterological and Pediatric Surgery, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan; (T.S.); (S.U.); (K.H.)
| | - Satoko Umetsu
- Department of Gasrtroenterological and Pediatric Surgery, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan; (T.S.); (S.U.); (K.H.)
| | - Akiko Igawa
- Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan; (C.U.); (Y.H.); (A.I.); (S.O.); (K.K.); (S.Y.)
- Department of Gasrtroenterological and Pediatric Surgery, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan; (T.S.); (S.U.); (K.H.)
| | - Sho Osonoi
- Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan; (C.U.); (Y.H.); (A.I.); (S.O.); (K.K.); (S.Y.)
| | - Kazuhiro Kudoh
- Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan; (C.U.); (Y.H.); (A.I.); (S.O.); (K.K.); (S.Y.)
| | - Yasuhiko Yamamoto
- Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8640, Japan; (Y.Y.); (H.Y.)
| | - Hiroshi Yamamoto
- Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8640, Japan; (Y.Y.); (H.Y.)
- Komatsu University, Komatsu 923-0921, Japan
| | - Soroku Yagihashi
- Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan; (C.U.); (Y.H.); (A.I.); (S.O.); (K.K.); (S.Y.)
| | - Kenichi Hakamada
- Department of Gasrtroenterological and Pediatric Surgery, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan; (T.S.); (S.U.); (K.H.)
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Oh J, Park HJ, Lee ES, Park SB, Choi BI, Ahn S. Severity of hyperechoic pancreas on ultrasonography as a risk factor for glycemic progression. Ultrasonography 2021; 40:499-511. [PMID: 33730774 PMCID: PMC8446494 DOI: 10.14366/usg.20122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Revised: 01/06/2021] [Accepted: 01/16/2021] [Indexed: 12/13/2022] Open
Abstract
PURPOSE The aim of this study was to evaluate the association between the severity of hyperechoic pancreas (HP) on ultrasonography (US) and glycemic progression. METHODS In total, 1,386 participants who underwent abdominal US as part of health examinations between December 2008 and May 2014 were included in this retrospective study. We classified pancreatic echogenicity on a 4-point scale, and compared it using two distinct criteria: fatty pancreas (FP) 1 criterion (normal vs. ≥mild HP) and FP2 criterion (normal/mild HP vs. ≥moderate HP). According to the presence of nonalcoholic fatty liver disease (NAFLD), participants were subdivided into four groups: non-NAFLD and non-HP, isolated NAFLD, isolated HP, and HP with NAFLD. Glycemic progression was defined as progression from normoglycemia to prediabetes or diabetes or progression from prediabetes to diabetes. RESULTS During the follow-up (median, 5.9 years), 262 of the 1,386 participants developed glycemic progression. Using FP2, the probability of glycemic progression across the four subgroups showed cumulative aggravation for NAFLD and HP (all P<0.05). Isolated HP showed a higher probability of glycemic progression than isolated NAFLD according to FP2 (P<0.001). The highest probability of glycemic progression was observed in patients with both NAFLD and HP (P<0.001). The hazard ratio for glycemic progression increased with the severity of HP. CONCLUSION Increasing severity of HP on US was found to be significantly correlated with glycemic progression. Moreover, isolated HP of moderate or greater severity predicted glycemic progression independent of NAFLD.
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Affiliation(s)
- Jiyun Oh
- Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea
| | - Hyun Jeong Park
- Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea
| | - Eun Sun Lee
- Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea
| | - Sung Bin Park
- Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea
| | - Byung Ihn Choi
- Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea
| | - Soohyun Ahn
- Department of Mathematics, Ajou University, Suwon, Korea
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Kobayashi N, Shinohara H, Haruta S, Udagawa H, Ueno M. Reducing the risk of postoperative pancreatic fistula in radical gastrectomy: pre-assessment with computed tomography for the diagnosis of pancreatic steatosis. Langenbecks Arch Surg 2021; 407:587-596. [PMID: 34559268 DOI: 10.1007/s00423-021-02337-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Accepted: 09/20/2021] [Indexed: 10/20/2022]
Abstract
PURPOSE To determine whether pancreatic steatosis (PS) is associated with the risk of postoperative pancreatic fistula (POPF) after radical gastrectomy, and if so, to investigate whether pre-assessment by diagnostic imaging can mitigate the risk. METHODS The clinical records of 276 patients with cStage I gastric cancer who underwent laparoscopic gastrectomy with D1 + lymphadenectomy between 2012 and 2015 were reviewed. In the first phase up to July 2013 (n = 138), PS was classified from computed tomography (CT) findings into type S (superficial fat deposition) or type D (diffuse fatty replacement) and examined for association with POPF. In the second phase (n = 138), the preoperative CT assessment of PS was routinized. Separate samples from pancreatoduodenectomy consistent with each type were histologically examined. RESULTS In the first phase, the incidence of POPF was significantly higher in group S, but not in group D, compared with normal pancreas (16.3% and 9.1% vs. 3.6%, respectively; P = 0.03). The drain amylase level was lowest in group D, reflecting exocrine insufficiency. Histologically, the loose connective-tissue space between the fat infiltrating the pancreas and the peripancreatic fat containing the lymph nodes was unclear in type D but conserved in type S. In the second phase, surgery was performed with more intention on accurately tracing the dissection plane and significantly lowered incidence of POPF in Group S (16.3% to 2.1%; P = 0.047). CONCLUSION Peripancreatic lymphadenectomy is more challenging and likely to cause POPF in patients with PS. However, the risk may be reduced using appropriate dissection techniques based on the CT pre-assessment findings.
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Affiliation(s)
- Nao Kobayashi
- Department of Surgery, Tsudanuma General Hospital, Narashino, Japan.,Department of Gastroenterological Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Hisashi Shinohara
- Department of Gastroenterological Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan. .,Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo, Japan.
| | - Shusuke Haruta
- Department of Gastroenterological Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Harushi Udagawa
- Department of Gastroenterological Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Masaki Ueno
- Department of Gastroenterological Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
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Abstract
As liver is one of the primary organs involved in glucose homeostasis, it is not surprising that patients with liver dysfunction in chronic liver disease usually develop impaired glucose tolerance and subsequently overt diabetes later in their natural course. Diabetes that develops after the onset of cirrhosis of liver is usually referred to as hepatogenous diabetes (HD). It is an underrecognized and a hallmark endocrinological event in chronic liver disease. HD is associated with a higher risk of developing hepatic decompensations, such as ascites, variceal bleeding, hepatic encephalopathy, renal dysfunction, refractory ascites, and hepatocellular carcinoma along with reduced survival rates than normoglycemic patients with cirrhosis of liver. It is quite different from type 2 diabetes mellitus with the absence of classical risk factors, dissimilar laboratory profiles, and decreased incidence of microvascular complications. Furthermore, the management of patients with HD is challenging because of altered pharmacokinetics of most antidiabetic drugs and increased risk of hypoglycemia and other adverse effects. Hence, a clear understanding of the epidemiology, pathophysiology, clinical implications, laboratory diagnosis, and management of HD is essential for both hepatologists as well as endocrinologists, which is narrated briefly in this review.
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Affiliation(s)
- Preetam Nath
- Department of Gastroenterology & Hepatology, Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha 751024, India
| | - Anil C. Anand
- Department of Gastroenterology & Hepatology, Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha 751024, India
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Swislocki A. Fatty Pancreas: An Underappreciated Intersection of the Metabolic Profile and Pancreatic Adenocarcinoma. Metab Syndr Relat Disord 2021; 19:317-324. [PMID: 33656378 DOI: 10.1089/met.2020.0070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Although the prevalence of pancreatic cancer is increasing, treatment strategies remain limited, and success is rare. A growing body of evidence links pancreatic cancer to pre-existing metabolic disorders, including, but not limited to, type 2 diabetes mellitus and obesity. An infrequently described finding, fatty pancreas, initially described in the context of obesity in the early 20th century, appears to be at the crossroads of type 2 diabetes and obesity on the one hand, and the development of pancreatic cancer on the other. Similarly, other conditions of the pancreas, such as intrapancreatic mucinous neoplasms, also seem to be related to diabetes while increasing the subsequent risk of pancreatic cancer. In this review, the author explores the diagnostic criteria for, and prevalence of, fatty pancreas and the potential link to other pancreatic conditions, including pancreatic cancer. Diagnostic limitations, and areas of controversy are also addressed, as are potential therapeutic approaches to fatty pancreas intended to reduce the subsequent risk of pancreatic cancer.
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Affiliation(s)
- Arthur Swislocki
- Medical Service (612/111), Veterans Affairs Northern California Health Care System (VANCHCS), Martinez, California, USA
- Department of Medicine, UC Davis School of Medicine, Sacramento, California, USA
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Pancreas morphogenesis and homeostasis depends on tightly regulated Zeb1 levels in epithelial cells. Cell Death Discov 2021; 7:138. [PMID: 34112759 PMCID: PMC8192546 DOI: 10.1038/s41420-021-00522-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Revised: 04/26/2021] [Accepted: 05/13/2021] [Indexed: 02/08/2023] Open
Abstract
The pancreas is comprised of exocrine and endocrine compartments releasing digestive enzymes into the duodenum and regulating blood glucose levels by insulin and glucagon release. Tissue homeostasis is depending on transcription factor networks, involving Ptf1α, Ngn3, Nkx6.1, and Sox9, which are already activated during organogenesis. However, proper organ function is challenged by diets of high sugar and fat content, increasing the risk of type 2 diabetes and other disorders. A detailed understanding of processes that are important for homeostasis and are impaired during type 2 diabetes is lacking. Here, we show that Zeb1—a transcription factor known for its pivotal role in epithelial-mesenchymal transition, cell plasticity, and metastasis in cancer—is expressed at low levels in epithelial cells of the pancreas and is crucial for organogenesis and pancreas function. Loss of Zeb1 in these cells result in an increase of islet mass, impaired glucose tolerance, and sensitizes to develop liver and pancreas steatosis during diabetes and obesity. Interestingly, moderate overexpression of Zeb1 results in severe pancreas agenesis and lethality after birth, due to islet insufficiency and lack of acinar structures. We show that Zeb1 induction interferes with proper differentiation, cell survival, and proliferation during pancreas formation, due to deregulated expression of endocrine-specific transcription factors. In summary, our analysis suggests a novel role of Zeb1 for homeostasis in epithelial cells that is indispensable for pancreas morphogenesis and proper organ function involving a tight regulation of Zeb1 expression.
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Ulasoglu C, Tekin ZN, Akan K, Yavuz A. Does Nonalcoholic Pancreatic Steatosis Always Correlate with Nonalcoholic Fatty Liver Disease? Clin Exp Gastroenterol 2021; 14:269-275. [PMID: 34149286 PMCID: PMC8205613 DOI: 10.2147/ceg.s317340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Accepted: 05/25/2021] [Indexed: 12/13/2022] Open
Abstract
PURPOSE To identify the correlation of nonalcoholic pancreatic steatosis (NAPS) with nonalcoholic fatty liver disease (NAFLD) in an outpatient group. Based on its metabolic and imaging properties, NAPS has been increasingly recognized in recent years; however, its interaction with NAFLD is still not clear. PATIENTS AND METHODS In this cross-sectional observational study, 345 consecutive patients without any chronic illness who were referred to the senior radiologist for abdominal ultrasound (US) were included. The US report showed hepatic and pancreatic echogenicity. The patients' demographic, anthropometric, and laboratory data were collected from medical records. RESULTS Overall, NAPS and NAFLD were seen in 227 (65.8%) and 219 (63.5%) patients, respectively. Normal echogenicity was noted in 74 (21.4%) patients. Forty-four patients (12.8%) had steatotic liver without NAPS, 52 (15.1%) had steatotic pancreas without NAFLD, and 175 (50.7%) had steatosis in both organs. The discordance in steatosis grading between NAPS and NAFLD was 55.1%. Insulin resistance was present in 8.7, 26.7, 19, and 61.3% of patients with no steatosis, only NAFLD, only NAPS, and steatosis in both organs, respectively. Evident NAFLD and NAPS having grade 2 and 3 steatosis were present in 15.3% and 29.0% of the study group, respectively. Cholecystolithiasis was present in 6.8, 13.6, and 28.8% of patients with normal echogenic pancreas, only NAFLD, and only NAPS, respectively (p=0.01). CONCLUSION Based on the ultrasonographic, clinical, demographic, and anthropometric features of the included patients, we found that NAPS did not fully accompany nonalcoholic fatty liver. Despite severe pancreatic steatosis, more than a quarter of cases had normal liver echogenicity. Insulin resistance frequency was insignificantly higher in NAFLD than NAPS (p=0.694). The significantly higher frequency of cholecystolithiasis in NAPS needs further large-scale studies. The inconsistency of steatosis degree in NAPS and NAFLD in >50% cases may reflect differences in the pathophysiology of these two clinical entities.
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Affiliation(s)
- Celal Ulasoglu
- Department of Gastroenterology, Medeniyet University, Goztepe Education and Research Hospital, Istanbul, Turkey
| | - Zeynep Nilufer Tekin
- Department of Radiology, Medeniyet University, Goztepe Education and Research Hospital, Istanbul, Turkey
| | - Kubra Akan
- Department of Gastroenterology, Medeniyet University, Goztepe Education and Research Hospital, Istanbul, Turkey
| | - Arda Yavuz
- Department of Gastroenterology, Medeniyet University, Goztepe Education and Research Hospital, Istanbul, Turkey
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Hoogenboom SA, Bolan CW, Chuprin A, Raimondo MT, van Hooft JE, Wallace MB, Raimondo M. Pancreatic steatosis on computed tomography is an early imaging feature of pre-diagnostic pancreatic cancer: A preliminary study in overweight patients. Pancreatology 2021; 21:428-433. [PMID: 33485792 DOI: 10.1016/j.pan.2021.01.003] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Revised: 12/07/2020] [Accepted: 01/07/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND The prevalence of pancreatic ductal adenocarcinoma (PDAC) is on the rise, driven by factors such as aging and an increasing prevalence of obesity and diabetes mellitus. To improve the poor survival rate of PDAC, early detection is vital. Recently, pancreatic steatosis has gained novel interest as a risk factor for PDAC. This study aimed to investigate if pancreatic steatosis on computed tomography (CT) is an early imaging feature in patients with pre-diagnostic PDAC. METHODS A retrospective case-control study was performed. Patients diagnosed with PDAC (2010-2016) were reviewed for abdominal non-contrast CT-imaging 1 month-3 years prior to their diagnosis. Cases were matched 1:4 with controls based on age, gender and imaging date. Unenhanced CT-images were evaluated for pancreatic steatosis (pancreas-to-spleen ratio in Hounsfield Units <0.70) by a blinded radiologist and results were compared between cases and controls. RESULTS In total, 32 cases and 117 controls were included in the study with a comparable BMI (29.6 and 29.2 respectively, p = 0.723). Pancreatic steatosis was present in 71.9% of cases compared to 45.3% of controls (Odds ratio (OR) 3.09(1.32-7.24), p = 0.009). Adjusted for BMI and diabetes mellitus, pancreatic steatosis on CT remained a significant independent risk factor for PDAC (Adjusted OR 2.70(1.14-6.58), p = 0.037). CONCLUSION Pancreatic steatosis measured on CT is independently associated with PDAC up to three years before the clinical diagnosis in overweight patients. If these data are confirmed, this novel imaging feature may be used to identify high-risk individuals and to stratify the risk of PDAC in individuals that already undergo PDAC screening.
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Affiliation(s)
- Sanne A Hoogenboom
- Department of Gastroenterology and Hepatology, Mayo Clinic Jacksonville, Florida, USA; Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
| | - Candice W Bolan
- Department of Radiology, Mayo Clinic Jacksonville, Florida, USA
| | - Anthony Chuprin
- Department of Radiology, Mayo Clinic Jacksonville, Florida, USA
| | - Maria T Raimondo
- Department of Gastroenterology and Hepatology, Mayo Clinic Jacksonville, Florida, USA
| | - Jeanin E van Hooft
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, Netherlands
| | - Michael B Wallace
- Department of Gastroenterology and Hepatology, Mayo Clinic Jacksonville, Florida, USA
| | - Massimo Raimondo
- Department of Gastroenterology and Hepatology, Mayo Clinic Jacksonville, Florida, USA
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The comparison of pancreatic and hepatic steatosis in healthy liver donor candidates. Sci Rep 2021; 11:4507. [PMID: 33627704 PMCID: PMC7904852 DOI: 10.1038/s41598-021-83871-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Accepted: 02/09/2021] [Indexed: 02/06/2023] Open
Abstract
The aim of this study was to investigate the relationship between nonalcoholic fatty liver disease (NAFLD) and pancreatic steatosis (PS) in patients with biopsy-proven NAFLD. 228 patients with biopsy-proven NAFLD patients who admitted to the Faculty of Medicine of Demiroglu Bilim University between 2004 and 2019 were included in the study. Demographic, laboratory, histological and radiological findings of the patients were recorded retrospectively. Hepatosteatosis (HS) levels were measured by both CT and biopsy, while PS levels were measured by 3 different CT-based techniques. 89 (39%) of the patients were female and 139 (61%) were male. The mean body mass index (BMI) was 27.2 ± 4.0. Biochemical parameters were within normal limits. Liver biopsy showed a significant correlation with HS grade on CT scan (p < 0.001). When CT findings were compared, a significant correlation was found between PS and HS (p < 0.05), but there was no correlation between the HS level in biopsy and the pancreatic adiposity on CT (p > 0.05). Our study was the first to compare biopsy-proven NAFLD and PS, and no correlation was found between biopsy-proven NAFLD and PS.
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e Silva LDLS, Fernandes MSDS, de Lima EA, Stefano JT, Oliveira CP, Jukemura J. Fatty Pancreas: Disease or Finding? Clinics (Sao Paulo) 2021; 76:e2439. [PMID: 33624707 PMCID: PMC7885852 DOI: 10.6061/clinics/2021/e2439] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Accepted: 12/27/2020] [Indexed: 12/22/2022] Open
Abstract
Despite a growing number of investigative studies on pancreatic fat deposition, there remains no clear indication regarding the clinical relevance of fat infiltration in the pancreas, also called fatty pancreas (FP). An individual's body weight is correlated with their pancreatic weight. Moreover, lipid infiltration causes disorders that compromise not only morphology but also metabolic functions. Fat infiltration leads to insulin resistance, type II diabetes mellitus, and pancreatic cancer; however, knowledge about pancreatic fat content and aspects related to the clinical profile remains unclear in the literature. The present review describes the current knowledge of FP, including its pathophysiology and clinical implications, as well as lifestyle changes in FP.
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Affiliation(s)
- Lucas de Lucena Simões e Silva
- Departamento de Gastroenterologia (LIM 07), Divisao de Gastroenterologia e Hepatologia, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
| | - Matheus Santos de Sousa Fernandes
- Programa de Pos Graduacao em Neuropsiquiatria e Ciencias do Comportamento, Departamento Educacao Fisica, Universidade Federal de Pernambuco, PE, BR
| | | | - José Tadeu Stefano
- Departamento de Gastroenterologia (LIM 07), Divisao de Gastroenterologia e Hepatologia, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
| | - Claudia P. Oliveira
- Departamento de Gastroenterologia (LIM 07), Divisao de Gastroenterologia e Hepatologia, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
| | - José Jukemura
- Departamento de Gastroenterologia Divisao de Cirurgia Digestiva, Instituto do Cancer (ICESP), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Faculdade de Medicina, Sao Paulo, SP, BR
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Wang F, So KF, Xiao J, Wang H. Organ-organ communication: The liver's perspective. Am J Cancer Res 2021; 11:3317-3330. [PMID: 33537089 PMCID: PMC7847667 DOI: 10.7150/thno.55795] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Accepted: 12/28/2020] [Indexed: 12/11/2022] Open
Abstract
Communication between organs participates in most physiological and pathological events. Owing to the importance of precise coordination among the liver and virtually all organs in the body for the maintenance of homeostasis, many hepatic disorders originate from impaired organ-organ communication, resulting in concomitant pathological phenotypes of distant organs. Hepatokines are proteins that are predominantly secreted from the liver, and many hepatokines and several signaling proteins have been linked to diseases of other organs, such as the heart, muscle, bone, and eyes. Although liver-centered interorgan communication has been proposed in both basic and clinical studies, to date, the regulatory mechanisms of hepatokine production, secretion, and reciprocation with signaling factors from other organs are obscure. Whether other hormones and cytokines are involved in such communication also warrants investigation. Herein, we summarize the current knowledge of organ-organ communication phenotypes in a variety of diseases and the possible involvement of hepatokines and/or other important signaling factors. This provides novel insight into the underlying roles and mechanisms of liver-originated signal transduction and, more importantly, the understanding of disease in an integrative view.
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Stolzenberg-Solomon RZ, Derkach A, Moore S, Weinstein S, Albanes D, Sampson J. Associations between metabolites and pancreatic cancer risk in a large prospective epidemiological study. Gut 2020; 69:2008-2015. [PMID: 32060129 PMCID: PMC7980697 DOI: 10.1136/gutjnl-2019-319811] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2019] [Revised: 01/17/2020] [Accepted: 01/20/2020] [Indexed: 12/15/2022]
Abstract
OBJECTIVE To assess whether prediagnostic metabolites were associated with incident pancreatic ductal adenocarcinoma (PDAC) in a prospective cohort study. DESIGN We conducted an untargeted analysis of 554 known metabolites measured in prediagnostic serum (up to 24 years) to determine their association with incident PDAC in a nested case-control study of male smokers (372 matched case-control sets) and an independent nested case-control study that included women and non-smokers (107 matched sets). Metabolites were measured using Orbitrap Elite or Q-Exactive high-resolution/accurate mass spectrometers. Controls were matched to cases by age, sex, race, date of blood draw, and follow-up time. We used conditional logistic regression adjusted for age to calculate ORs and 95% CIs for a 1 SD increase in log-metabolite level separately in each cohort and combined the two ORs using a fixed-effects meta-analysis. RESULTS Thirty-one metabolites were significantly associated with PDAC at a false discovery rate <0.05 with 12 metabolites below the Bonferroni-corrected threshold (p<9.04×10-5). Similar associations were observed in both cohorts. The dipeptides glycylvaline, aspartylphenylalanine, pyroglutamylglycine, phenylalanylphenylalanine, phenylalanylleucine and tryptophylglutamate and amino acids aspartate and glutamate were positively while the dipeptides tyrosylglutamine and α-glutamyltyrosine, fibrinogen cleavage peptide DSGEGDFXAEGGGVR and glutathione-related amino acid cysteine-glutathione disulfide were inversely associated with PDAC after Bonferroni correction. Five top metabolites demonstrated significant time-varying associations (p<0.023) with the strongest associations observed 10-15 years after participants' blood collection and attenuated thereafter. CONCLUSION Our results suggest that prediagnostic metabolites related to subclinical disease, γ-glutamyl cycle metabolism and adiposity/insulin resistance are associated with PDAC.
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Affiliation(s)
- Rachael Z. Stolzenberg-Solomon
- Metabolic Epidemiology Branch, Division Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, United States
| | - Andriy Derkach
- Biostatistics Branch, Division Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, United States
| | - Steven Moore
- Metabolic Epidemiology Branch, Division Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, United States
| | - Stephanie Weinstein
- Metabolic Epidemiology Branch, Division Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, United States
| | - Demetrius Albanes
- Metabolic Epidemiology Branch, Division Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, United States
| | - Joshua Sampson
- Biostatistics Branch, Division Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, United States
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Fang T, Huang S, Chen Y, Chen Z, Chen J, Hu W. Glucagon Like Peptide-1 Receptor Agonists Alters Pancreatic and Hepatic Histology and Regulation of Endoplasmic Reticulum Stress in High-fat Diet Mouse Model. Exp Clin Endocrinol Diabetes 2020; 129:625-633. [PMID: 32961563 DOI: 10.1055/a-1240-4936] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND Obesity is a major health problem worldwide, and non-alcoholic fatty pancreas disease (NAFPD) and non-alcoholic fatty liver disease (NAFLD) are obesity-associated complications. Liraglutide, a glucagon-like peptide-1 (GLP-1) agonist, has been approved for treatment of obesity. We aimed to evaluate the therapeutic effects of liraglutide on the complications through its regulation of endoplasmic reticulum (ER) stress. METHODS A high-fat diet mouse model was established in C57BL/6J mice. Two groups of mice were fed a high-fat diet with 60% fat for 16 weeks and control mice were fed standard chow. A four-week 0.6 mg/kg/day liraglutide treatment was started in one high-fat diet group after 12 weeks of the high-fat diet. After sacrificing the mice, pancreatic and hepatic tissues were prepared for western blot and immunohistochemistry for ER stress proteins, including activating transcription factor 4 (ATF4), caspase 12, C/EBP homologous protein (CHOP) eukaryotic initiation factor 2 α (eIF2α), glucose regulated protein (GRP) 78 and protein kinase RNA-like endoplasmic reticulum kinase (PERK). RESULTS Liraglutide significantly decreased body weight gained by mice consuming a high-fat diet (27.6 g vs. 34.5 g, P<0.001), and levels of all ER proteins increased significantly in both the pancreas and liver (all P<0.05). Expression of most ER stress proteins in pancreatic tissue correlated with disease scores of NAFLD (all P<0.05). However, no significant differences were found in pancreatic ATF 4 expression between mice without NAFLD, and those with early non-alcoholic steatohepatitis (NASH) and fibrotic NASH (P=0.122). CONCLUSION Liraglutide reduces the severity of NAFPD and NAFLD may through regulating the ER stress pathway and downstream apoptosis signaling.
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Affiliation(s)
- Taiyong Fang
- Department of Gastroenterology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China
| | - Siying Huang
- Department of Gastroenterology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China
| | - Yongpeng Chen
- Department of Gastroenterology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China
| | - Zongchi Chen
- Department of Gastroenterology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China
| | - Jiangmu Chen
- Department of Gastroenterology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China
| | - Weitao Hu
- Department of Gastroenterology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China
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